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This study- a secondary analysis of data from a randomized, observer-blinded, non-inferiority study among volunteers between 18-55 y old in Türkiye- evaluated the impact of previous SARS-CoV-2 infection before the first dose of inactive TURKOVAC on post-vaccine local and systemic adverse events (AEs) comparing with CoronaVac. Of 1266 participants analyzed, 27.7% had a previous COVID-19 history. Local and systemic AEs were observed in 37.3% and 39% of the participants. The frequency of AEs was slightly higher in the first 30 minutes and 24 hours among participants with a COVID-19 history; none were severe. 1203 participants had a second dose vaccination, and 27.3% had a history of COVID-19. The frequencies of local and systemic AEs after the second dose were similar between those with and without a COVID-19 history. The TURKOVAC and CoronaVac showed similar frequencies of local and systemic AEs in the first 30 minutes after vaccination.

The interaction between Nitisinone (NTBC) and bovine serum albumin (BSA) as the transport protein in a circulating system was investigated for the first time utilizing various analytical (UV-Vis spectrophotometry, fluorescence spectroscopy, dynamic light scattering, and differential scanning calorimetry) and computational (molecular docking and molecular dynamics simulations) methods. The BSA fluorescence intensity was quenched upon interaction with NTBC, and the quenching mechanism was observed as static. The interaction between NTBC and BSA was examined at 288 K, 298 K, and 308 K where the binding constants were found to be 1.44 × 10 5  ± 0.22 M -1 , 5.18 × 10 4  ± 0.20 M -1 , and 3.02 × 10 4  ± 0.22 M -1 respectively, suggesting an intermediate binding affinity between NTBC and BSA. Changes in the microenvironment surrounding tryptophan and tyrosine residues of BSA were elucidated using 3-D fluorescence spectroscopy. Thermodynamic studies revealed the calculated values of ΔH =  - 54.34 ± 5 kJ/mol and ΔS =  - 0.0908 ± 0.24 kJ/mol K -1 , indicating the involvement of van der Waals forces and hydrogen bonds in the interaction between NTBC and BSA. Moreover, the interaction's spontaneous nature was evidenced by negative ΔG values across all temperatures. Using dynamic light scattering, it was observed that higher NTBC concentrations led to a gradual rise in hydrodynamic diameter and notable aggregation of the NTBC-BSA complex. Moreover, changing signal values and shifted peaks of BSA, NTBC, and complex in differential scanning calorimetry curves, meant there were molecular interactions between the NTBC and BSA. In silico approaches also elucidated how NTBC binds to active sites on BSA, further supporting other findings. Moreover, molecular docking studies offer a more profound insight into the changing dynamics of hydrophobic, hydrogen, and halogen bonding involved in stabilizing the NTBC-BSA complex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose of Review: The rate of inborn errors of immunity (IEI) in the Middle East and North Africa (MENA) region is generally higher than in other parts of the world. IEI patients in MENA exhibit more severe disease phenotypes. One of the most important reasons for this is delayed diagnosis. In this review, we examine issues pertinent to primary, secondary, and tertiary physicians in diagnosing IEI in children and discuss the key points for pediatricians according to the MENA guideline., Recent Findings: Protocols and stepwise approaches designed by a panel of clinical immunologists included in the MENA-IEI registry network can help physicians facilitate the diagnosis of patients with IEI by providing recommendations. These recommendations for diagnostic approaches improve the care of patients within the MENA region and can also be applied to IEI patients in other parts of the world other regions., Summary: Physicians in the MENA region should be aware of IEI, obtain a detailed family history, request tests that can be ordered in primary care when IEI is suspected, and refer patients to clinical immunologists without delay. Primary and secondary care physicians should be aware that patients with IEI may present with noninfectious manifestations and increased infection frequency, severity, and atypical infections., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

End-of-life management of copper indium gallium selenide (CIGS) thin-film solar photovoltaics (PV) panels is crucial due to the necessity of recycling valuable elements such as indium ($400/kg) and gallium ($618/kg), ensuring both economic viability and environmental sustainability. In this study, we analyze the private and external costs of end-of-life management for CIGS PV designed for mass-scale recycling. Our findings reveal that the private and external costs of end-of-life management range from ∼$3.5 to $4.5 and ∼$3.0 to $4.0 per m 2 , respectively. The chemicals utilized in the recycling process, particularly NaOH and HCl, significantly contribute to climate change, photochemical oxidant formation, particulate matter formation, and freshwater eutrophication impact categories, accounting for ∼50 % to 90 % of the impacts. Furthermore, we found the net cost of recycling by subtracting the economic benefit obtained from recovered materials from the sum of private and external costs, revealing values ranging between $4.3 and $5.7 per m 2 of CIGS PV module. These findings suggest that there is room to reduce the net cost further by recovering more materials from the CIGS PV modules components., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ilke Celik reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF-α and IL-6 by 75.22% and 82.51%, respectively. It elevated the caspase-3 level by 7.21-fold. Furthermore, IC50 against COX-I, COX-II, and VEGFR-2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs., (© 2024 Wiley‐VCH GmbH.)

Background: Although the gold standard for diagnosing beta-lactam antibiotic (BLA) allergy is the drug provocation test (DPT), there is no standardized protocol for children. Objective: We aimed to evaluate the clinical features and DPT results of children with a history of low-risk non-immediate reactions (NIR) to BLA who underwent initial direct single therapeutic dose challenge with a 5-day prolonged DPT. Methods: We retrospectively evaluated children ages 0-18 years with a history of low-risk NIRs to BLAs. On the first day of provocation, a single-dose DPT protocol without any skin test was administered at the clinic. The therapeutic dose was adjusted to not exceed the maximum single-unit dose (MSUD) for age and weight. The DPT protocol was administered with 100% of MSUD. To identify children with delayed reactions, the parents or caregivers were told to continue giving the medication at home for 5 days. Results: One hundred and nine children were included in this study. The median (interquartile range) age of the children was 62.5 months (26.5-94 months). Of the suspected drugs, the main culprit drug was amoxicillin-clavulanic acid for 89 children (81.7%). The most common clinical manifestation was maculopapular exanthema, which occurred in 85 children (78%), and 8 (7.3%) had a positive DPT result. Three children (2.8%) developed a reaction after the first DPT dose. The remaining children continued to use the suspected BLA at home. Five children (4.7%) developed a reaction while using the drug at home. All the children with positive DPT results developed mild cutaneous signs and presented with a reaction to amoxicillin-clavulanic acid. None had a systemic or severe cutaneous reaction. Conclusion: Initial direct single therapeutic dose challenge with a 5-day prolonged DPT is a useful and safe way to assess low-risk NIRs to BLAs in children.

This study investigated the effect of Urtica dioica roots etheric extract (UDEE) on oxidative stress, and urine obstruction with histopathological examinations of prostatic and renal tissues,and suggests computational methods as a complementary method, to make a hypothesis on the overall effect of UDEE in the treatment of benign prostatic hyperplasia (BPH).Gas chromatography/mass spectrometry was utilised to characterise UDEE.BPH was induced in rats through daily subcutaneous injections of testosterone propionate. Rats were also orally administered UDEE or a vehicle. After four weeks, prostate weight, urine output, and biochemical markers were evaluated. UDEE treatment demonstrated significant regression of prostatic enlargement, improved biochemical and histopathological characteristics, and regulation of antioxidant activity levels. Phytosteroids stand out, act by inhibiting 5α-reductase and aromatase. This study provides an insight into treatment of BPH, demonstrating safety of this compound towards the kidney compared to finasteride without severe side effects.

Apraclonidine (APR) is a potent and selective α2-adrenergic receptor agonist used in the diagnosis of Horner's Syndrome, and the residuals of APR that accumulate in tissues of animals can cause central nervous and cardiovascular systems influences in humans. Therefore, to understand the influence of APR on human health, we examined the interaction of APR with the carrier protein in plasma, bovine serum albumin (BSA). The BSA fluorescence signal was quenched due to the APU-BSA complex formation and a weak binding affinity was estimated between APR and BSA. The inclusion of fluorescence, UV-vis absorption, molecular docking, and dynamics simulation techniques employed to broadly investigate the combination of APR with BSA at typical physiological conditions. The thermodynamic results revealed that enthalpy (ΔH 0 ) and entropy (ΔS 0 ) changes were computed as +11.14 kJ mol -1 and +97.56 J mol -1 K -1 , respectively, which represented the binding is principally entropy-driven and the hydrophobic forces acting a significant role in the reaction. Analysis of synchronous and 3-D fluorescence signals revealed microenvironmental variations close to BSA's Trp and Tyr residues upon APR addition. Both the competitive site marker as well as molecular docking results detected that APR exhibited a stronger binding affinity towards Drug Site 2 (DS2) compared to Drug Site 1 (DS1)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: Primary immunodeficiencies (PIDs) are a heterogeneous disorder group characterized by an impaired immune system, leading to an increased susceptibility to infections and a wide range of clinical manifestations, including gastrointestinal (GI) complications. This study aimed to assess the GI manifestations of PID patients and highlight the significance of atypical gastrointestinal symptoms in the early diagnosis of these patients., Methods: A retrospective analysis was conducted on pediatric patients diagnosed with PIDs at Selcuk University Medical Faculty from 2011 to 2021. The study focused on demographic data, clinical presentation, genetic mutations, and GI manifestations, including endoscopic evaluation. Patients were categorized according to the International Union of Immunological Societies (IUIS) PID classifications. Statistical analyses were performed to identify significant associations between PID types and GI manifestations., Results: The cohort comprised 101 patients, with 46% presenting with GI symptoms, including malnutrition and chronic diarrhea, as the most common findings. Primary antibody deficiency (PAD) emerged as the most prevalent PID with GI involvement, followed by combined immunodeficiencies (CID) with associated or syndromic features. Endoscopic evaluations revealed inflammatory bowel disease (IBD)-like colitis in a significant subgroup of patients. The analysis showed that some GI symptoms were more common in specific PID categories, highlighting the importance of early gastroenterological assessment in PID patients., Conclusion: Recognition of common GI symptoms in pediatric patients with PIDs may facilitate early diagnosis and prompt multidisciplinary management, potentially improving patient outcomes. The study highlights the necessity of considering PIDs in diagnosing persistent or severe GI symptoms in children.

Aim: This study aims to adapt the "Nursing Practice Readiness Scale" to Turkish culture, and evaluate its psychometric properties., Background: New graduates' nursing practice readiness can impact their work adaptation and performance., Design: The research employed a methodological design., Methods: Data were collected between May and July 2022. The sample consisted of 436 newly graduated nurses. Content validity, construct validity and criterion validity were evaluated. Reliability was examined with adjusted item-total correlation, Cronbach's a coefficient, composite-reliability and split-half reliability., Results: The Turkish version of Nursing Practice Readiness Scale was found to have good content and criterion validity. As a result of confirmatory factor analysis, the original five-factor structure of the scale was also confirmed for the Turkish version. The scale's overall Cronbach's α coefficient was determined to be 0.96, with subscale coefficients ranging from 0.73 to 0.94. The composite reliability values of the subscales were found between 0.75 and 0.94. In split-half reliability, the correlation coefficient between half was 0.952, with a Spearman-Brown Coefficient (Unequal Length) of 0.976., Conclusions: The Turkish version of Nursing Practice Readiness Scale is a valid and reliable measurement tool for evaluating the nursing practice readiness of newly graduated nurses., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: The aim of this study was to evaluate the biocompatibility and effectiveness in terms of osseointegration of dental implants composed of novel injectable bone grafts with and without ostrich eggshell particles and membrane protein in rabbit femur., Methods: Sixteen adult male New Zealand rabbits were used in this study. A bone defect was created in each animal's right and left femur, and a dental implant was placed adjacent to the defect. Two graft materials were prepared, one containing the membrane protein and the other not. In two groups, the defects were filled with these materials. In the negative control group (NC, (n:8)), the defects were left empty. A commercial product of biphasic calcium sulfate was used as a positive control material (PC, n = 8). The graft groups were defined as the group with the membrane protein (MP+, (n:8)), and without the membrane protein (MP-, n:8). The animals were euthanized at the 12th week after surgery. The samples were investigated using histology, histomorphometry, and micro-computed tomography. Data were statistically analyzed using one-way ANOVA and Tukey's tests ( p = 0.05)., Results: Both the PC and MP+ groups had similar newly formed bone areas, and the mean values of these groups were significantly ( p < 0.05) higher than those of the MP- and NC groups. The PC group had the highest amount of unresorbed material, while the MP- group had the lowest amount of unresorbed material. The bone-implant contact (BIC) scores of the PC and MP+ groups were significantly higher ( p < 0.05) than that of the NC group. The connective tissue area of the PC group was the lowest, which was significantly lower than the other groups ( p < 0.05)., Conclusions: The grafts produced are highly biocompatible and also showed osteoproductivity. Their cost-effectiveness and osteoproductive activity require further investigation.

Cannabinoids bind to cannabinoid receptors CB1 and CB2 and their antitumoral activity has been reported against some various cancer cell lines. Some synthetic cannabinoids possessing indole rings such as JWH-015 and JWH-133 particularly bind to the cannabinoid CB2 receptor and it was reported that they inhibit the proliferation and growth of various cancer cells without their psychoactive effects. However, the pharmacological action mechanisms of the cannabinoids are completely unknown. In this study, we report the synthesis of some new cannabinoidic novel indoles and evaluate their anticancer activity on various cancerous and normal cell lines (U87, RPMI 8226, HL60 and L929) using several cellular and molecular assays including MTT assay, real-time q-PCR, scratch assay, DAPI assay, Annexin V-PE/7AAD staining, caspase3/7 activity tests. Our findings indicated that compounds 7, 10, 13, 16, and 17 could reduce cell viability effectively. Compound 17 markedly increased proapoptotic genes (BAX, BAD, and BIM), tumor suppressor gene (p53) expression levels as well as the BAX/BCL-2 ratio in U87 cells. In addition, 17 inhibited cell migration. Based on these results, 17 was chosen for determining the mechanism of cell death in U87 cells. DAPI and Annexin V-7AAD staining results showed that 17 induced apoptosis, moreover activated caspase 3/7 significantly. Hence, compound 17, was selected as a lead compound for further pharmacomodulation. To rationalize the observed biological activities of 17, our study also included a comprehensive analysis using molecular docking and MD simulations. This integrative approach revealed that 17 fits tightly into the active site of the CB2 receptor and is involved in key interactions that may be responsible for its anti-proliferative effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We report herein, the design and synthesis of benzimidazole-oxadiazole derivatives as new inhibitors for vascular endothelial growth factor receptor-2 (VEGFR-2). The designed members were assessed for their in vitro anticancer activity against three cancer cell lines and two normal cell lines; A549, MCF-7, PANC-1, hTERT-HPNE and CCD-19Lu. Compounds 4c and 4d were found to be the most effective compounds against three cancer cell lines. Compounds 4c and 4d were then tested for their in vitro VEGFR-2 inhibitory activity, safety profiles, and selectivity indices using the normal hTERT-HPNE and CCD-19Lu cell lines. It was determined that compound 4c was the most effective and safe member of the produced chemical family. Vascular endothelial growth factor A (VEGFA) immunolocalizations of compounds 4c and 4d were evaluated relative to control by VEGFA immunofluorescence staining. Compounds 4c and 4d inhibited VEGFR-2 enzyme with half-maximal inhibitory concentration values of 0.475 ± 0.021 and 0.618 ± 0.028 µM, respectively. Molecular docking of the target compounds was carried out in the active site of VEGFR-2 (Protein Data Bank: 4ASD)., (© 2024 The Author(s). Drug Development Research published by Wiley Periodicals LLC.)

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC 50 = 2.49 μM) and has demonstrated selectivity towards FLT3 ITD-mutated MV4-11 AML cells, with an IC 50 of 4.3 μM. By utilizing the scaffold of the previous hit, sixteen new compounds were synthesized and screened against NCI-60 human cancer cell lines. This leads to the discovery of a potent antiproliferative compound, namely 5l , with an average GI 50 value against leukemia and colon cancer subpanels equalling 3.39 and 5.97 µM, respectively. Screening against a specific set of 10 kinases that are associated with carcinogenesis indicates that compound 5l has a potent FLT3 inhibition (IC 50 = 36.21 ± 1.07 nM). Remarkably, compound 5l was three times more effective as a CDK2 inhibitor (IC 50 = 8.17 ± 0.32 nM) compared to sunitinib (IC 50 = 27.90 ± 1.80 nM). Compound 5l was further analyzed by means of docking and molecular dynamics simulation for CDK2 and FLT3 active sites which provided a rational for the observed strong inhibition of kinases. These results suggest a novel structural scaffold candidate that simultaneously inhibits CDK2 and FLT3 and gives encouragement for further development as a potential therapeutic for leukemia and colon cancer.

Objectives: To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent., Methods: Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics., Key Findings: Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively., Conclusions: Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Background: Multidrug-resistant Acinetobacter baumannii is still a major contributor to outbreaks and infections health care-associated infections. This study aimed to investigate an outbreak of wound infection due to A baumannii in trauma patients injured in the Kahramanmaraş earthquake., Methods: This retrospective case-control study was conducted on an outbreak of wound infection caused by A. baumannii in trauma patients affected by the February 6 Turkey earthquake. Among the patients who underwent at least one extremity surgery due to earthquake-related crush-trauma injury, patients with wound infection due to A baumannii were included in the case group and without infection were included in the control group. Multivariate analysis and logistic regression were performed to identify risk factors. Environmental cultures were taken to identify the source of the outbreak. Molecular typing by pulsed-field gel electrophoresis was used to confirm the relationships of the wound infection agent A. baumannii strains., Results: A total of 44 patients were included in the case group and 62 patients in the control group. Time under the debris; 22.0 versus 35.7 (odds ratio [OR]:1.02, 95% confidence interval [CI]: 1.00-1.04) and hemodialysis (OR: 6.09, 95% CI: 1.64-22.66) were identified as risk factors for in the multivariate analysis. Performing the first intervention in a fully equipped tertiary hospital was seen as an infection-reducing factor compared to performing it in a field hospital (OR: 0.21, 95% CI: 0.06-0.68). Dressing trolleys and scissors were identified as the source of the outbreak., Conclusions: After devastating earthquakes, a large number of patients are admitted and require emergency interventions due to life-threatening conditions. Organ failure often develops and requires the use of invasive catheters and procedures. Compliance with infection control measures and clean surgical interventions reduce wound site infections and allow extremities to heal, while problems in adhering to infection control measures can lead to many problems such as outbreaks of gram-negative bacteria. This highlights the importance of infection control measures., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: There are limited data regarding the characteristics and management of drug hypersensitivity reactions (DHR) in hospitalized children. This study aims to determine the prevalence, clinical features, and management of DHRs in pediatric inpatients., Methods: Children who had pediatric allergy consultation for suspected DHR during hospitalization in Ankara Bilkent City Hospital between August 1, 2020, and July 30, 2021, were included. Patient and reaction characteristics, culprit drugs, and management strategies were recorded. When possible, diagnostic tests (skin or provocation tests) were performed after discharge., Results: Among the 14,090 hospitalized children, 165 (72% male, median age: 106 months) underwent consultation for 192 suspected DHRs with 246 drugs. Cutaneous eruptions were the most common (94.3%). There was anaphylaxis in 40 patients and severe cutaneous adverse drug reaction in 4 patients (drug rash with eosinophilia and systemic symptoms in 3, acute generalized exanthematous pustulosis in 1). Antimicrobials were the leading cause (78.4%, n = 193/246). In 48 reactions, 60 (24%) culprit drugs could be readministered with close follow-up or desensitization (n = 12). In total, 186 suspected drugs were discontinued, and 115 were replaced with alternative drugs. After discharge, 38 provocation tests (2 positives) and 36 skin tests (1 positive prick test, 1 positive intradermal test, and 1 positive patch test) were performed., Discussion/conclusions: The incidence of suspected DHR among pediatric inpatients was approximately 1.1%. Skin symptoms were the most common manifestation. Twenty-four percent of suspected drugs could be continued during hospitalization. Patients with DHR during hospitalization should be evaluated with a drug allergy work-up unless there are contraindications to testing., (© 2024 The Authors.)

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a - h were characterized using 1 H NMR, 13 C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC 50 value of 7.34 ± 0.21 μM and 4.56 ± 0.18 μM, respectively. These results were compared to standard drugs, doxorubicin (IC 50 = 12.420 ± 0.5 μM) and Hoechst 33342 (IC 50 = 0.422 ± 0.02 μM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (Δ E = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The current study's objective was to investigate how an antifungal pesticide Azoxystrobin (AZO) interacts with bovine serum albumin (BSA) under conditions that simulate a physiological medium (pH 7.4). This investigation was carried out using various experimental (UV-Vis absorption, steady-state fluorescence and 3-D fluorescence spectroscopies, and electrochemical) and theoretical (molecular docking and molecular dynamics simulations) methods. The fluorescence quenching data demonstrated that AZO caused fluorescence quenching in BSA, and this quenching process was attributed to the static quenching mechanism. By examining the fluorescence quenching of BSA at three different temperatures, it was determined that the binding constants for the AZO-BSA complexes were approximately 10 4 M -1 in magnitude, while the same magnitude of the binding constant was found by the electrochemical method. This indicates that the interaction between AZO and BSA was of moderate strength. This was further validated by the changes observed in the UV-Vis spectrum of BSA following the addition of AZO. The thermodynamic information, including ΔH and ΔS, revealed that the interaction forces primarily involved van der Waals forces as well as hydrogen bonds. The negative Gibbs free energy indicated that the reaction is spontaneous. In the theoretical investigation, the comparison highlights a remarkable consistency in how AZO interacts with the BSA active site over various time points. Hydrogen bonding and hydrophobic interactions consistently play a role in ensuring the stable and specific binding of the ligand. Moreover, the 3-D fluorescence spectral findings revealed alterations in the surrounding microenvironment of protein fluorophores when AZO binds. Upon analyzing the electrochemical data, it was observed that there was a consistent decrease in the peak currents of AZO when BSA was added to solutions containing AZO. The primary cause of this decrease in the peak currents was the reduction in the equilibrium concentration of AZO due to the addition of BSA. Furthermore, the formation of a non-electroactive complex between BSA and AZO, which impedes electron transport between AZO and the working electrode, accounts for these decreases. As a result, it can be said that the understanding of how AZO binds to BSA offers valuable insights that can be applied in the food, human health, and environment sectors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Land use competition between agricultural activities and ground-mounted solar photovoltaic (PV) deployment has increased worldwide attention to hybrid agriculture, and PV systems known as agrivoltaic systems (AVS) in efforts to increase the efficiency of energy and food production and minimize the land use competition. However, little is known about AVS's economic feasibility and environmental tradeoffs. Here we aim to evaluate the techno-economic and environmental impacts of four AVS configurations (full density, half density, mono-axial tracking, and bi-axial tracking) and compare their performance against PV-only systems. We used the life cycle revenue generated from a hectare of land area ($/ha) as a functional unit of our analysis. We found that all AVS configurations outperformed PV-only systems in the economic feasibility assessment, where bi-axial tracking was the best-performing AVS. Further, we developed a case scenario for agricultural farmers to determine the minimum selling price of electricity required for AVS to compete with the economic performance of crop-only farms. We found that the AVS designs require additional incentives (2¢ - 6¢ per kWh of electricity generation) to be as competitive as the crop-only farms. The life cycle environmental assessment demonstrated that the AVS has better environmental performance than PV-only systems, with ∼15-55 % less environmental impacts per functional unit. On average, electricity generation accounts for ∼80 % of AVS environmental impacts, while food production and water demand account for ∼20 %. Additionally, a sensitivity analysis conducted on various uncertain parameters, such as crop yield, water demand, electricity selling price, crop selling prices, discount, and inflation rates, while varying these parameters across broader ranges, indicates that AVS designs become a more economically and environmentally sustainable alternative over PV-only systems in the majority (>66 %) of the data analyzed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A series of alkylsulfonyl 1 H -benzo[ d ]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 in vitro . The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds. The results revealed that compounds 23 and 27 were the most potent cytotoxic derivatives against MCF-7 cells. Gene expression analysis showed that BCL-2 was the most prominent gene studied. Treatment of MCF-7 cells with compounds 23 and 27 resulted in significant downregulation of the BCL-2 gene, with fold changes of 128 and 256, respectively. Docking analysis predicted a strong interaction between the compounds and the target protein. Interestingly, all of the compounds exhibit a higher binding affinity toward Bcl-2 than the standard drug (compound 27 vina score = -9.6 kcal/mol, vincristine = -6.7 kcal/mol). Molecular dynamics simulations of compounds 23 and 27 showed a permanent stabilization in the binding site of Bcl-2 for 200 ns. Based on Lipinski and Veber's filters, all synthesized compounds displayed drug-like characteristics. These findings suggest that compounds 23 and 27 were the most promising cytotoxic compounds and downregulated the expression of the BCL-2 gene. These derivatives could be further explored as potential candidates for the treatment of breast cancer., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study., Methods: Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC-MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented., Results: Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC 50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site., Conclusion: The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination., (© 2024. The Author(s).)

Pineapple has been recognized for its potential to enhance health and well-being. This study aimed to gain molecular insights into the anti-inflammatory properties of fermented pineapple juice using multimodal computational studies. In this study, pineapple juice was fermented using Lactobacillus paracasei, and the solution underwent liquid chromatography-mass spectrometry analysis. Network pharmacology was applied to investigate compound interactions and targets. In silico methods assessed compound bioactivities. Protein-protein interactions, network topology, and enrichment analysis identified key compounds. Molecular docking explored compound-receptor interactions in inflammation regulation. Molecular dynamics simulations were conducted to confirm the stability of interactions between the identified crucial compounds and their respective receptors. The study revealed several compounds including short-chain fatty acids, peptides, dihydroxyeicosatrienoic acids, and glycerides that exhibited promising anti-inflammatory properties. Leucyl-leucyl-norleucine and Leu-Leu-Tyr exhibited robust and stable interactions with mitogen-activated protein kinase 14 and IκB kinase β, respectively, indicating their potential as promising therapeutic agents for inflammation modulation. This proposition is grounded in the pivotal involvement of these two proteins in inflammatory signaling pathways. These findings provide valuable insights into the anti-inflammatory potential of these compounds, serving as a foundation for further experimental validation and exploration. Future studies can build upon these results to advance the development of these compounds as effective anti-inflammatory agents., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

The emergence of multidrug resistance (MDR) in bacterial pathogens is a serious public health concern. A significant therapeutic target for MDR infections is the quorum sensing-regulated bacterial pathogenicity. Determining the anti-quorum sensing abilities of certain medicinal plants against bacterial pathogens as well as the in-silico interactions of particular bioactive phytocompounds with QS and biofilm-associated proteins were the objectives of the present study. In this study, 6 medicinal plants were selected based on their ethnopharmacological usage, screened for Anti-QS activity and Artemisia annua leaf extract (AALE) demonstrated pigment inhibitory activity against Chromobacterium violaceum CV12472. Further, the methanol active fraction significantly inhibited the virulence factors (pyocyanin, pyoverdine, rhamnolipid and swarming motility) of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 at respective sub-MICs. The inhibition of biofilm was determined using a microtiter plate test and scanning electron microscopy. Biofilm formation was impaired by 70%, 72% and 74% in P. aeruginosa, C. violaceum and S. marcescens, respectively at 0.5xMIC of the extract. The phytochemical content of the extract was studied using GC-MS and 1, 8-cineole was identified as major bioactive compound. Furthermore, 1, 8-cineole was docked with quorum sensing (QS) proteins (LasI, LasR, CviR, and rhlR) and biofilm proteins (PilY1 and PilT). In silico docking and dynamics simulations studies suggested interactions with QS-receptors CviR', LasI, LasR, and biofilm proteins PilY1, PilT for anti-QS activity. Further, 1, 8-cineole demonstrated 66% and 51% reduction in violacein production and biofilm formation, respectively to validate the findings of computational analysis. Findings of the present investigation suggests that 1, 8-cineole plays a crucial role in the QS and biofilm inhibitory activity demonstrated by Artemisia annua extract. RESEARCH HIGHLIGHTS: Artemisia annua leaf extract (AALE) methanol fraction demonstrated broad-spectrum QS and biofilm inhibition Scanning electron microscopy (SEM) confirmed biofilm inhibition Molecular docking and simulation studies suggested positive interactions of 1,8-cineol with QS-receptors and biofilm proteins., (© 2023 Wiley Periodicals LLC.)

The quorum sensing mechanism relies on the detection and response to chemical signals, termed autoinducers, which regulate the synthesis of virulence factors including toxins, enzymes, and biofilms. Emerging therapeutic strategies for infection control encompass approaches that attenuate quorum-sensing systems. In this study, we evaluated the antibacterial, anti-quorum sensing, and anti-biofilm activities of Psidium guajava L. methanolic leaf extracts (PGME). Minimum Inhibitory Concentrations (MICs) of PGME were determined as 500 μg/ml for C. violaceum and 1000 μg/ml for P. aeruginosa PAO1. Significantly, even at sub-MIC concentrations, PGME exhibited noteworthy anti-quorum sensing properties, as evidenced by concentration-dependent inhibition of pigment production in C. violaceum 12742. Furthermore, PGME effectively suppressed quorum-sensing controlled virulence factors in P. aeruginosa PAO1, including biofilm formation, pyoverdin, pyocyanin, and rhamnolipid production, with concentration-dependent inhibitory effects. Phytochemical analysis utilizing GC-MS revealed the presence of compounds such as alpha-copaene, caryophyllene, and nerolidol. In-silico docking studies indicated a plausible mechanism for the observed anti-quorum sensing activity, involving favorable binding and interactions with QS-receptors, including RhlR, CviR', LasI, and LasR proteins. These interactions were found to potentially disrupt QS pathways through suppression of AHL production and receptor protein blockade. Collectively, our findings propose PGME as a promising candidate for the treatment of bacterial infections. Its attributes that mitigate biofilm development and impede quorum-sensing mechanisms highlight its potential therapeutic value., Competing Interests: NO authors have competing interests., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The ongoing concern surrounding coronavirus disease 2019 (COVID-19) primarily stems from continuous mutations in the genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to the emergence of numerous variants. The receptor-binding domain (RBD) in the S1 subunit of the S protein of the virus plays a crucial role in recognizing the host's angiotensin-converting enzyme 2 (hACE2) receptor and facilitating cell membrane fusion processes, making it a potential target for preventing viral entrance into cells. This research aimed to determine the potential of banana lectin (BanLec) proteins to inhibit SARS-CoV-2 attachment to host cells by interacting with RBD through computational modeling., Materials and Methods: The BanLecs were selected through a sequence analysis process. Subsequently, the genes encoding BanLec proteins were retrieved from the Banana Genome Hub database. The FGENESH online tool was then employed to predict protein sequences, while web-based tools were utilized to assess the physicochemical properties, allergenicity, and toxicity of BanLecs. The RBDs of SARS-CoV-2 were modeled using the SWISS-MODEL in the following step. Molecular docking procedures were conducted with the aid of ClusPro 2.0 and HDOCK web servers. The three-dimensional structures of the docked complexes were visualized using PyMOL. Finally, molecular dynamics simulations were performed to investigate and validate the interactions of the complexes exhibiting the highest interactions, facilitating the simulation of their dynamic properties., Results: The BanLec proteins were successfully modeled based on the RNA sequences from two species of banana (Musa sp.). Moreover, an amino acid modification in the BanLec protein was made to reduce its mitogenicity. Theoretical allergenicity and toxicity predictions were conducted on the BanLecs, which suggested they were likely non-allergenic and contained no discernible toxic domains. Molecular docking analysis demonstrated that both altered and wild-type BanLecs exhibited strong affinity with the RBD of different SARS-CoV-2 variants. Further analysis of the molecular docking results showed that the BanLec proteins interacted with the active site of RBD, particularly the key amino acids residues responsible for RBD's binding to hACE2. Molecular dynamics simulation indicated a stable interaction between the Omicron RBD and BanLec, maintaining a root-mean-square deviation (RMSD) of approximately 0.2 nm for a duration of up to 100 ns. The individual proteins also had stable structural conformations, and the complex demonstrated a favorable binding-free energy (BFE) value., Conclusions: These results confirm that the BanLec protein is a promising candidate for developing a potential therapeutic agent for combating COVID-19. Furthermore, the results suggest the possibility of BanLec as a broad-spectrum antiviral agent and highlight the need for further studies to examine the protein's safety and effectiveness as a potent antiviral agent., (© 2023. The Author(s).)

As a part of our continuous effort to find new therapeutic agents from natural sources, the hydroalcoholic (1:1) extract of Citrus maxima (Burm.) Merr. root was selected for the identification of possible antimalarial phytoconstituents. From the extract, three flavonoids including luteolin were isolated and evaluated for in vitro antimalarial activity against the chloroquine-sensitive ( Pf 3D7) and resistant ( Pf RKL-9) strains of Plasmodium falciparum . Among these, luteolin (CM3) showed the highest antimalarial activity with IC 50 values of 2.315 ± 0.489 and 2.691 ± 0.454 µg/ml against the Pf 3D7 and Pf RKL-9 strains respectively. To assess the safety of luteolin (CM3), a cytotoxicity study against a normal human embryonic kidney cell line (HEK-293) was performed and the compound was found to be safe with a CC 50 value of 222.3 ± 1.443 µg/ml. The docking study against 26 target proteins of P. falciparum revealed that luteolin (CM3) has a better binding affinity with two proteins, viz. P. falciparum lactate dehydrogenase ( Pf LDG) and P. falciparum enoyl-ACP reductase ( Pf EAR) in comparison to the co-crystallized ligands. Furthermore, the molecular dynamics simulation study of the protein-ligand complexes also supported the binding affinity and interactions of luteolin (CM3) at the active sites. Finally, the binding free energy calculation revealed that the luteolin formed a thermodynamically more stable complex with Pf LDG (-50.955 ± 17.184 kJ/mol) than Pf EAR (-24.856 ± 13.739 kJ/mol). Overall, in this study, we identified an antimalarial marker in the hydroalcoholic extract of C. maxima root which may act by inhibiting Pf LDG.Communicated by Ramaswamy H. Sarma.

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory., (© 2023. The Author(s).)

Objective: This study aimed to demonstrate the relationship between thorax computed tomography (CT) findings at the time of admission and prognosis using a semiquantitative CT severity scoring system in patients diagnosed with coronavirus disease 2019 (COVID-19) who tested positive for reverse transcriptase polymerase chain reaction (RT-PCR)., Patients and Methods: A total of 305 patients aged 18 years and older who were diagnosed with COVID-19 confirmed by RT-PCR and underwent thorax CT at the time of admission, were included in the study between March and July 2020. The demographic data of the patients, their presenting complaints at the time of admission, RT-PCR results, and thorax CT images were scanned retrospectively from electronic medical records. Lesions on thorax CT were evaluated for the presence of ground glass opacity, consolidation, and septal thickening and scoring., Results: No significant relationship was found between mortality and CT score or other parameters. A significant relationship was found between admission to the intensive care unit and CT scoring (p=0.014), aortic diameter (p=0.032), chronic pulmonary disease (p=0.004), halo sign (p=0.031), mortality (p<0.001), fever (p=0.038), and dyspnea (p=0.031). A statistically significant difference was detected in the score parameter between discharged patients and intensive care unit patients who survived and those who died (p<0.001). In the parameter of the number of lobes, a statistically significant difference was found only between discharged patients and intensive care unit patients who survived (p=0.016)., Conclusions: Thorax CT is an advisor for early diagnosis, treatment, and prognosis assessment of the disease. Semiquantitative CT severity scoring can provide valuable information about the prognosis of the patient.

Background: Cancer is one of the leading causes of death worldwide. Recently, it was shown that many natural extracts have positive effects against cancer, compared with chemotherapy or recent hormonal treatments. A. annua is an annual medicinal herb used in the traditional Chinese medicine. It has also been shown to inhibit the proliferation of various cancer cell lines., Methods: Multi-level modes of action of A. annua constituents in cancer therapy were investigated using an integrated approach of network pharmacology, molecular docking, dynamic simulations and in-vitro cytotoxicity testing on both healthy and cancer cells., Results: Network pharmacology-based analysis showed that the hit Artemisia annua constituents related to cancer targets were 3-(2-methylpropanoyl)-4-cadinene-3,11-diol, artemisinin G, O-(2-propenal) coniferaldehyde, (2-glyceryl)-O-coniferaldehyde and arteamisinin III, whereas the main cancer allied targets were NFKB1, MAP2K1 and AR. Sixty-eight significant signaling KEGG pathways with p < 0.01 were recognized, the most enriched of which were prostate cancer, breast cancer, melanoma and pancreatic cancer. Thirty-five biological processes were mainly regulated by cancer, involving cellular response to mechanical stimulus, positive regulation of gene expression and transcription. Molecular docking analysis of the top hit compounds against the most enriched target proteins showed that 3-(2-methylpropanoyl)-4-cadinene-3,11-diol and O-(2-propenal) coniferaldehyde exhibited the most stabilized interactions. Molecular dynamics simulations were performed to explain the stability of these two compounds in their protein-ligand complexes. Finally, confirmation of the potential anticancer activity was attained by in-vitro cytotoxicity testing of the extract on human prostate (PC-3), breast (MDA-MB-231), pancreatic (PANC-1) and melanoma (A375) cancerous cell lines., Conclusion: This study presents deeper insights into A. annua molecular mechanisms of action in cancer for the first time using an integrated approaches verifying the herb's value., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Seeds are widely consumed as a traditional snack and have rich contents beneficial to health. With an increase in consumption rates, allergic reactions occur more frequently. We focus on multiple seed consumption related to recurrent anaphylaxis in this case. Case Presentation: We evaluated an 11-year-old boy with recurrent anaphylaxis. According to his medical records, he had been hospitalized several times, diagnosed with anaphylaxis, and treated. The family noticed direct (eating) or indirect contact with pumpkin seeds. In addition, the family mentioned another anaphylactic episode after watermelon seed and poppy seed bread consumption. We conducted skin prick-to-prick tests, examined total immunoglobulin E levels, and prescribed the treatment with an adrenalin autoinjector and preventive dietary recommendations. Conclusion: Anaphylaxis, particularly recurrent ones, should be evaluated with detailed anamnesis and supported with laboratory tests. Although seeds are beneficial and highly nutritious, it is necessary to consider them a source of allergens.

Background: The drug provocation test (DPT) and the oral food challenge (OFC) are considered as the criterion standard for the diagnosis of drug hypersensitivity reactions and food allergy. Severe allergic reactions may develop during these tests. Objective: To evaluate the frequency and features of anaphylaxis in pediatric patients undergoing OFCs and DPTs. Method: OFCs and DPTs performed in an open method in the pediatric allergy clinic of our institution between January 2014 and January 2021 were reviewed retrospectively. The characteristics of anaphylaxis that developed during these tests were evaluated. Results: A total of 3631 OFCs and/or DPTs were performed on 2588 pediatric patients. Reactions were recorded in 317 challenges (8.7%), including 42 (1.2%) in the form of anaphylaxis. Of the patients with anaphylaxis, 31 developed anaphylaxis during OFC and 11 during DPT. Anaphylaxis during OFCs was mostly triggered by yogurt (n = 8), hen's egg (n = 6), baked milk (n = 5), and baked egg (n = 4). Cases with anaphylaxis during DPT were recorded mostly with ibuprofen (54.5% [n = 6]). All patients who developed anaphylaxis during OFC had cutaneous manifestations, and 90.3% had respiratory symptoms. Gastrointestinal involvement was present in 32.3% of the patients. During DPT, cutaneous manifestations were observed in 90.9% in the patients who developed anaphylaxis and the respiratory tract was involved in 81.8%. In terms of concomitant allergic diseases, 51.6% of the patients who developed anaphylaxis during OFC had atopic dermatitis and 38.7% had asthma. All the patients with anaphylaxis triggered by nonsteroidal anti-inflammatory drug DPT had asthma. Of the anaphylaxis, 54.8% were mild, 35.7% were moderate, and 9.5% were severe. Severe anaphylaxis was recorded with baked milk (n = 2), baked egg and trimethoprim-sulfamethoxazole (n = 1, each). The patients did not require intensive care, and no death occurred. Conclusion: Anaphylaxis may develop during OFCs and DPTs. These tests should be carried out by experienced allergists in an appropriate setting where emergency equipment and medications, including epinephrine, are readily available.

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging nosocomial pathogen among hospitalized patients, with high morbidity and mortality rates. The discovery of a novel antibacterial is urgently needed to address this resistance problem. The present study aims to explore the antibacterial potential of three depsidone compounds: 2-clorounguinol ( 1 ), unguinol ( 2 ), and nidulin ( 3 ), isolated from the marine sponge-derived fungus Aspergillus unguis IB1, both in vitro and in silico . The antibacterial activity of all compounds was evaluated by calculating the Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against MRSA using agar diffusion and total plate count methods, respectively. Bacterial cell morphology changes were  studied for the first time using scanning electron microscopy (SEM). Molecular docking, pharmacokinetics analysis, and molecular dynamics simulation were performed to determine possible protein-ligand interactions and the stability of the targeting penicillin-binding protein 2a (PBP2a) against 2-clorounguinol ( 1 ). The research findings indicated that compounds 1 to 3 exhibited MIC and MBC values of 2 µg/mL and 16 µg/mL against MRSA, respectively. MRSA cells displayed a distinct shape after the addition of the depsidone compound, as observed in SEM. According to the in silico study, 2-chlorounguinol exhibited the highest binding-free energy (BFE) with PBP2a (-6.7 kcal/mol). For comparison, (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid inhibits PBP2a with a BFE less than -6.6 kcal/mol. Based on the Lipinski's rule of 5, depsidone compounds constitute a class of compounds with good pharmacokinetic properties, being easily absorbed and permeable. These findings suggest that 2-chlorounguinol possesses potential antibacterial activity and could be developed as an antibiotic adjuvant to reduce antimicrobial resistance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.

Introduction: Most melanoma patients under our supervision lack characteristic phenotypic features for melanoma. In contrast, history of cancers other than melanoma and early age at onset were common. This observation was in favor of hereditary melanoma., Objectives: To search for the phenotypic and genetic features that differ between sporadic and hereditary melanomas., Methods: In order to reveal phenotypic features, detailed physical exam was conducted to all melanoma patients (N = 43) and for genetic features. CDKN2A and MC1R mutations were detected with Sanger sequencing method. Assignment to hereditary and sporadic groups was done according to the "melanoma cancer syndrome assessment tool". Patients who were diagnosed before the age of 50 were also assigned to the hereditary melanoma group., Results: Thirty-one patients were assigned to the hereditary group and 12 to the sporadic group. Fair eye color was statistically significantly higher in the sporadic group (P = 0.000). CDKN2A was detected in only 1 patient in the hereditary group. MC1R mutations were found in 12 out of 13 (92.3%) in the hereditary group with a score =3 points, 13 out of 18 (72.2%) in the early age at onset group and 5 out of 12 (41.7%) in the sporadic group (P = 0.024)., Conclusions: Incidence of CDKN2A mutations in our hereditary group is in accordance with the reported incidences from Mediterranean countries. The difference between the hereditary and sporadic groups in terms of MC1R mutations supports the idea that MC1R genetic testing might help to determine patients with higher risk for hereditary melanoma.

Theoretical analyses of two phenothiazine derivatives, 10-[3-(dimethylamino)-2-methylpropyl]phenothiazine-2-carbonitrile (CYM) and 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol (PAZ) are reported using density functional theory (DFT) and molecular dynamics (MD) simulations. Spectroscopic studies, different electronic and chemical parameters are predicted. Red and yellow in electrostatic potential plot is in rings and oxygen atom in PAZ and C≡N and rings in CYM are sensitive to nucleophilic attacks. The blue in hydrogen atoms refer to electrophilic attack in both PAZ and CYM. Stability of the protein-ligand complex formed with these derivatives and angiotensin-converting enzyme 2 (ACE2) was investigated using MD simulation. Radius of gyration of C-alpha atom of 6VW1 displayed the conformational convergence toward a compact structure leading to stable 6VW1-ligand complex which are also in agreement with root mean square fluctuation (RMSF) values. Localized area predicts reactive sites for Au and H 2 O molecules interaction with these compounds for further practical applications. Charge density is localized on both molecules and also tries to move toward Au-Au dimer and water molecule and such they are expected to contribute to the sensing performance.Communicated by Ramaswamy H. Sarma.

Pyrazolo[4,3- e ]tetrazolo[1,5- b ][1,2,4]triazine sulfonamides ( MM -compounds) are a relatively new class of heterocyclic compounds that exhibit a wide variety of biological actions, including anticancer properties. Here, we used caspase enzyme activity assays, flow cytometry analysis of propidium iodide (PI)-stained cells, and a DNA laddering assay to investigate the mechanisms of cell death triggered by the MM -compounds ( MM134 , -6 , -7 , and -9 ). Due to inconsistent results in caspase activity assays, we have performed a bromodeoxyuridine (BrdU) incorporation assay, colony formation assay, and gene expression profiling. The compounds' cytotoxic and pro-oxidative properties were also assessed. Additionally, computational studies were performed to demonstrate the potential of the scaffold for future drug discovery endeavors. MM-compounds exhibited strong micromolar (0.06-0.35 µM) anti-proliferative and pro-oxidative activity in two cancer cell lines (BxPC-3 and PC-3). Activation of caspase 3/7 was observed following a 24-h treatment of BxPC-3 cells with IC 50 concentrations of MM134 , -6, and -9 compounds. However, no DNA fragmentation characteristics for apoptosis were observed in the flow cytometry and DNA laddering analysis. Gene expression data indicated up-regulation of BCL10, GADD45A, RIPK2, TNF, TNFRSF10B, and TNFRSF1A (TNF-R1) following treatment of cells with the MM134 compound. Moreover, in silico studies indicated AKT2 kinase as the primary target of compounds. MM -compounds exhibit strong cytotoxic activity with pro-oxidative, pro-apoptotic, and possibly pro-necroptotic properties that could be employed for further drug discovery approaches.

Centaurea lycaonica is a local endemic species from the Centaurea L. genus. The Centaurea species has a wide range of usage in treating diseases in folk medicine. There are limited biological activity studies on this species in the literature. This study investigated enzyme inhibition and antimicrobial activity, antioxidant effect, and chemical content of extract and fractions of C. lycaonica . Enzyme inhibition activity was tested by α-amylase, α-glucosidase, and tyrosinase enzyme inhibition methods and antimicrobial activity by the microdilution method. The antioxidant activity was investigated using DPPH • , ABTS •+ , and FRAP tests. The chemical content was determined by LC-MS/MS. The methanol extract showed the highest activity for α-glucosidase and α-amylase, even surpassing the positive control acarbose, with IC 50 values of 56.333 ± 0.986 and 172.800 ± 0.816 μg/mL, respectively. Additionally, the ethyl acetate fraction also exhibited high activity for α-amylase with an IC 50 value of 204.067 ± 1.739 μg/mL and tyrosinase with an IC 50 value of 213.900 ± 1.553 μg/mL. Moreover, this extract and fraction were found to have the highest total phenolic and flavonoid contents and antioxidant activity. Additionally, LC-MS/MS analyses of active extract and fraction revealed mainly the presence of phenolic compounds and flavonoids. In silico molecular docking and molecular dynamics simulation studies of determining compounds apigenin and myristoleic acid, common in CLM and CLE extracts and active against α-glucosidase and α-amylase, were performed. In conclusion, methanol extract and ethyl acetate fraction showed potential enzyme inhibition and antioxidant activity as a natural agent. Molecular modeling studies corroborate the findings of in vitro activity analyses., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Most synthetic immunomodulatory medications are extremely expensive, have many disadvantages and suffer from a lot of side effects. So that, introducing immunomodulatory reagents from natural sources will have great impact on drug discovery. Therefore, this study aimed to comprehend the mechanism of the immunomodulatory activity of some natural plants via network pharmacology together with molecular docking and in vitro testing. Apigenin, luteolin, diallyl trisulfide, silibinin and allicin had the highest percentage of C-T interactions while, AKT1, CASP3, PTGS2, NOS3, TP53 and MMP9 were found to be the most enriched genes. Moreover, the most enriched pathways were pathways in cancer, fluid shear stress and atherosclerosis, relaxin signaling pathway, IL-17 signaling pathway and FoxO signaling pathway. Additionally, Curcuma longa, Allium sativum, Oleu europea, Salvia officinalis, Glycyrrhiza glabra and Silybum marianum had the highest number of P-C-T-P interactions. Furthermore, molecular docking analysis of the top hit compounds against the most enriched genes revealed that silibinin had the most stabilized interactions with AKT1, CASP3 and TP53, whereas luteolin and apigenin exhibited the most stabilized interactions with AKT1, PTGS2 and TP53. In vitro anti-inflammatory and cytotoxicity testing of the highest scoring plants exhibited equivalent outcomes to those of piroxicam., (© 2023. The Author(s).)

Developing modifiable natural products those having antiviral activities against SARS-CoV-2 is a key research area which is popular in current scenario of COVID pandemic. A diaryl heptanoid curcumin and its derivatives are already presenting promising candidates for anti-viral drug development. We have synthesized single crystals of a dimethylamino derivative of natural curcumin and structural characterization was done by single crystal XRD analysis. Using steady-state absorption and emission spectra and guided by complimentary ab initio calculations, we unraveled the solvent effects on the photophysical properties of the dimethyl amino curcumin derivative. Chemical reactivity of the compound has investigated using frontier molecular orbitals and molecular electrostatic potential surface. High stability of the curcumin derivative in water environment has evaluated by Radial Distributions Functions (RDF) calculated via Molecular Dynamics (MD) simulations. The inhibitory activity of the title compound was evaluated by in silico methods and the stability of the protein-ligand complexes were studied using Molecular Dynamics simulations and MM-PBSA analysis. With this detailed study, we hope to motivate scientific community to develop new curcumin derivatives against SARS-CoV-2 virus., Competing Interests: All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue., (© 2023 Elsevier B.V. All rights reserved.)

Benzimidazole-1,3,4-oxadiazole derivatives (5a-z) were synthesized and characterized with different spectroscopic techniques such as 1 H NMR, 13 C NMR, and HRMS. The synthesized analogs were examined against α-glucosidase and α-amylase enzymes to determine their antidiabetic potential. Compounds 5g and 5q showed the most activity with 35.04 ± 1.28 and 47.60 ± 2.16 µg/mL when compared with the reference drug acarbose (IC 50  = 54.63 ± 1.95 µg/mL). Compounds 5g, 5o, 5s, and 5x were screened against the α-amylase enzyme and were found to show excellent potential, with IC 50 values ranging from 22.39 ± 1.40 to 32.07 ± 1.55 µg/mL, when compared with the standard acarbose (IC 50  = 46.21 ± 1.49 µg/mL). The antioxidant activities of the effective compounds (5o, 5g, 5s, 5x, and 5q) were evaluated by TAS methods. A molecular docking research study was conducted to identify the active site and explain the functions of the active chemicals. To investigate the most likely binding mode of the substances 5g, 5o, 5q, 5s, and 5x, a molecular dynamics simulation was also carried out., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

The significant increase in the human population and the associated industrial wastes have a widespread impact on coastal areas. It is important to monitor trace elements that affect food safety and pose a potential consumer health threat. All over the Black Sea coast, people enjoy consuming whiting as both meat and roe. In February 2021, whitings were caught by bottom trawling from four different locations on the coasts of Kastamonu, Sinop (Sarıkum, Adabaşı), and Samsun in the southern Black Sea region. The meat and roe extracts obtained from whiting samples were analyzed through an optical emission spectrophotometer (ICP-MS). Trace element concentrations of whiting meat and roe in this study were Zn > Fe > Sr > As > Al > Se > B > Mn > Cu > Hg > Li > Ni > Ba > Pb > Cr > Cd and Zn > Fe > Al > As > Cu > Sr > Mn > Se > B > Ba > Li > Ni > Hg > Cr > Pb > Cd, respectively. These amounts were lower than the acceptable values accepted by the EU Commission. In case of whiting and roe consumption of a maximum of three portions (860.33 g) for Adabaşı, six portions for Kastamonu (1432.37 g), three portions for Samsun (828.55 g), and five portions (1253.04 g) for Sarıkum per month do not pose a health risk., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nerium oleander L. is ethnopharmacologically used for diabetes. Our aim was to investigate the ameliorative effects of ethanolic Nerium flower extract (NFE) in STZ-induced diabetic rats., Methods: Seven random groups including control group, NFE group (50 mg/kg), diabetic group, glibenclamide group and NFE treated groups (25 mg/kg, 75 mg/kg, and 225 mg/kg) were composed of forty-nine rats. Blood glucose level, glycated hemoglobin (HbA1c), insulin level, liver damage parameters and lipid profile parameters were investigated. Antioxidant defense system enzyme activities and reduced glutathione (GSH) and malondialdehyde (MDA) contents and immunotoxic and neurotoxic parameters were determined in liver tissue. Additionally, the ameliorative effects of NFE were histopathologically examined in liver. mRNA levels of SLC2A2 gene encoding glucose transporter 2 protein were measured by quantitative real time PCR., Results: NFE caused decrease in glucose level and HbA1c and increase in insulin and C-peptide levels. Additionally, NFE improved liver damage biomarkers and lipid profile parameters in serum. Moreover, lipid peroxidation was prevented and antioxidant enzyme activities in liver were regulated by NFE treatment. Furthermore, anti-immunotoxic and anti-neurotoxic effects of NFE were determined in liver tissue of diabetic rats. Histopathogically, significant liver damages were observed in the diabetic rats. Histopathological changes were decreased partially in the 225 mg/kg NFE treated group. SLC2A2 gene expression in liver of diabetic rats significantly reduced compared to healthy rats and NFE treatment (25 mg/kg) caused increase in gene expression., Conclusion: Flower extract of Nerium plant may have an antidiabetic potential due to its high phytochemical content., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The present study was designed to investigate the effects of Rheum ribes L. plant root extracts on DNA damage, biochemical and antioxidant parameters in rats with experimental obesity induced with a high-calorie diet. The study groups were divided as "normal control(NC)", "obese control(OC)", "obese + Rheum ribes (OR1)(200 mg/kg)" and "obese + Rheum ribes (OR2)(400 mg/kg)". At the end of the application, rats were sacrificed and blood and tissue samples were obtained. According to the results obtained, the marker of DNA damage in tissues of 8-OHdG was determined to be significantly reduced in brain tissue of the OR1 and OR2 groups compared to the NC group. However, fluctuations were identified in the MDA activity, antioxidant defense system elements and serum biomarkers in tissues. In conclusion, Rheum ribes plant root extract ensured improvements in DNA damage in brain tissues and MDA levels and showed positive effects on antioxidant parameter activities in different tissues.

OBJECTIVE: β-Elemene, a sesquiterpene with a broad anti-cancer spectrum, is particularly effective against drug-resistant and complex tumors. It can also be efficient against FLT3-expressed acute myeloid leukemia. This research aims to determine whether β-Elemene has cytotoxic effects on FLT3 ITD-mutated AML cells. MATERIALS AND METHODS: Cytotoxicity, cell morphology, mRNA analysis with apoptotic markers, and analysis of 43 distinct protein markers related to cell death, survival, and resistance were all performed to elucidate its mechanism. Additionally, in order to understand how β-Elemene and FLT3 interact, molecular docking, molecular dynamics simulations, and computational ADME investigations were performed. RESULTS: β-Elemene exhibited cytotoxic activity against FLT3-mutated MV4-11 and FLT3 wild-type THP-1 cells, with an IC50 of around 25 µg/ml. The molecular studies revealed that β-Elemene inhibited cell proliferation by inducing p53, and the involvement of p21, p27, HTRA, and HSPs were also demonstrated. The interactive inhibition in proliferation was confirmed via molecular docking and dynamics analyses. β-Elemene occupied the FLT3 enzymatic pocket with good stability at the FLT3 active site. CONCLUSIONS: We concluded from our observations that β-Elemene causes cell death in ITD mutant AML cells, together with the effects of stress factors and inhibiting cell division.

Continuous monitoring of the population's health is the main method of learning about disease prevalence. National and international data draw attention to the persistently high rates of cancer incidence. This necessitates the intensification of efforts aimed at developing new, more effective chemotherapeutic and chemopreventive drugs. Plants represent an invaluable source of natural substances with versatile medicinal properties. Multidirectional activities exhibited by natural substances and their ability to modulate key signaling pathways, mainly related to cancer cell death, make these substances an important research direction. This review summarizes the information regarding plant-derived chemotherapeutic drugs, including their mechanisms of action, with a special focus on selected anti-cancer drugs (paclitaxel, irinotecan) approved in clinical practice. It also presents promising plant-based drug candidates currently being tested in clinical and preclinical trials (betulinic acid, resveratrol, and roburic acid).

Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6- O -benzylidene-α-d-glucopyranoside (MBG) derivatives ( 2 - 7 ). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4 , 5 , 6 and 7 . The compounds with the most significant antifungal efficacy were 4 , 5 , 6 and 7 . Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure-activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH 3 (CH 2 ) 10 CO-), cinnamoyl-(C 6 H 5 CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1 δ- ----O2 δ- ) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Breast cancer is the most frequent female cancer and second cause of cancer-related deaths among women around the world. Two thirds of breast cancer patients have hormone-dependent tumors, which is very likely be treated with hormonal therapy. Aromatase is involved in the biosynthesis of estrogen thus a critical target for breast cancer. In this study, in order to identify new aromatase enzyme inhibitors, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC 50 values of 5.165 ± 0.211 μM and 5.995 ± 0.264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a , in silico molecular docking and dynamics simulations against aromatase enzyme was performed to determine possible protein-ligand interactions and stability. DFT study was performed to evaluate the quantum mechanical and electronic properties of compound 5a . Finally, the theoretical ADME properties of the potential aromatase inhibitor compound 5a were analyzed by calculations.Communicated by Ramaswamy H. Sarma.