Search

Muhammad Shahid Nazir,1 Matloob Ahmad,1 Sana Aslam,2 Ayesha Rafiq,1 Sami A Al-Hussain,3 Magdi EA Zaki3 1Department of Chemistry, Government College University, Faisalabad, Pakistan; 2Department of Chemistry, Government College Women University, Faisalabad, Pakistan; 3Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi ArabiaCorrespondence: Matloob Ahmad; Magdi EA Zaki, Email Matloob.Ahmad@gcuf.edu.pk; mezaki@imamu.edu.saAbstract: The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins. Keywords: COVID-19, SARS-CoV-2, heterocyclic nucleus, in vitro, in silico, molecular docking studies

Shazia Naheed,1 Irum Umar Din,1 Muhammad Usman Qamar,2 Nasir Rasool,1 Matloob Ahmad,1 Muhammad Bilal,1 Aqsa Khalid,3 Gulraiz Ahmad,1 Sami A Al-Hussain,4 Magdi EA Zaki4 1Department of Chemistry, Government College University Faisalabad, Faisalabad, 38000, Pakistan; 2Institute of Microbiology, Faculty of Life Sciences, Government College University, Faisalabad, 38000, Pakistan; 3School of Interdisciplinary Engineering & Science (SINES), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan; 4Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyad, 11623, Saudi ArabiaCorrespondence: Nasir Rasool; Magdi E A Zaki, Email nasirrasool@gcuf.edu.pk; mezaki@imamu.edu.saIntroduction: Global public health concerns include the emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase Escherichia coli (ESBL-E. coli). These pathogens cause infections that are difficult to treat, which can have fatal outcomes and require lengthy hospital stays. As a result, we created butyl 2-bromoisonicotinate and tested its antibacterial effectiveness against the ESBL-E. coli ST 405 and MRSA pathogens. Natural product discovery is complemented by synthetic compound synthesis because of the latter’s potential for superior characteristics, target specificity, scalability, intellectual advantages, and chemical diversity. Because of this, the potential for discovering new medicinal compounds is increased, and the constraints placed on natural sources are overcome. Natural items are tough to obtain since they are hard to isolate and synthesize. Therefore, modern science is actively searching for small molecules as therapeutic agents by applying sustainable techniques that can be commercialized.Methods: Two patients’ blood samples were taken, and the BACTEC/Alert system was used to process them. On blood and MacConkey agar, the positive samples were subcultured and incubated aerobically at 37 °C. Using the VITEK 2 compact system, the isolates were subjected to isolate identification and MIC. MLST of the ESBL-E. coli was performed by PCR. Additionally, Fischer esterification was used to create butyl 2-bromoisonicotinate in excellent yields. A commercially available palladium catalyst was then used to arylate the compound, resulting in medium to good yields of arylated butyl 2-bromoisonicotinates. Using the agar well diffusion assay and the micro-broth dilution method, we assessed the in-vitro activities of the synthesized molecules (3, 5a-h) against clinically isolated ESBL-E. coli ST405, and MRSA. A molecular operating environment was used to carry out in silico validation of the synthesized compounds’ binding to the active site and to evaluate the stability of their molecular interactions with the target E. coli 2Y2T protein.Results: MRSA and ESBL-producing E. coli were identified as the two clinical isolates. While MRSA was also resistant to beta-lactam drugs and least resistant to vancomycin, ESBL-producing E. coli belonged to ST405 and was resistant to cephalosporins and sensitive to carbapenems. Good yields of the desired compounds were produced by our effective and economical synthesis. By using a micro-broth dilution assay, the Molecules (3, 5a, and 5d) were most effective against both resistant strains. The Molecules (3, 5a, 5b, and 5d) also displayed good binding energies.Conclusion: The butyl 2-bromoisonicotinate displayed antibacterial efficacy against ESBL-producing E. coli ST405 and MRSA strains. After the in-vivo trial, this substance might offer an alternative therapeutic option.Keywords: ESBL, MRSA, MLST, Fischer esterification, Suzuki-Miyaura, docking studies

Refaie M Kassab,1 Sami A Al-Hussain,2 Nooran S Elleboudy,3 Amgad Albohy,4 Magdi EA Zaki,2 Khaled AM Abouzid,5,6 Zeinab A Muhammad7 1Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt; 2Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia; 3Department of Microbiology and Immunology, The Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt (BUE), Cairo, 11837, Egypt; 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt; 6Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt; 7Department of Organic Chemistry, National Organization for Drug Control and Research (NODCAR), Giza, 12311, EgyptCorrespondence: Refaie M Kassab, Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt, Tel +20101-336-2594, Fax +20-25685799, Email rkassab@sci.cu.edu.eg Sami A Al-Hussain, Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia, Email sahussain@imamu.edu.saIntroduction: Antibiotic resistance is a global threat that has been increasing recently, especially with antibiotic overuse and misuse. The search for new antibiotics is becoming more and more indispensable.Methods: Design and synthesis of isatin derivatives as surrogates of SB-239629, a bacterial tyrosine-tRNA synthetases (TyrRS) inhibitor. The newly synthesized compounds were screened for their antimicrobial and antibiofilm activities. Docking studies were used to investigate potential binding modes of these compounds with TyrRS.Results and Discussion: Newly synthesized isatin-decorated thiazole derivatives (7b, 7d, and 14b) have shown potent antimicrobial activities against E. coli, a representative of gram-negative bacteria. Also, 7f showed the best activity against Methicillin Resistant Staphylococcus aureus (MRSA). In addition, 7h and 11f were found to have antifungal activities against Candida albicans equivalent to that of the reference Nystatin. All the new isatin derivatives with antimicrobial activities were found to exhibit strong biofilm distortion effects at half their minimum inhibitory concentrations (MIC). Moreover, thiazole derivatives 11a-f showed promising biofilm formation inhibition. Finally, molecular docking studies were used to investigate possible binding modes of target compounds with S. aureus and E. coli TyrRS.Conclusion: The novel isatin-decorated thiazole derivatives show strong antimicrobial and antifungal activities with potential action on TyrRS.Keywords: 5-bromoisatin, thiosemicarbazone, hydrazonoyl chlorides, thiazoles, Tyrosyl-tRNA synthetases (TyrRS) inhibitors, antimicrobial, molecular docking, MRSA, antibiofilm

Wound healing is a complex physiological process, demanding advanced strategies for efficient tissue regeneration. To address this, we developed a novel nanofibrous matrix composed of polygalacturonic acid (PGA), polyvinyl alcohol (PVA), capsaicin, and zinc-doped mesoporous silica (Zn/MCM-41). This copolymeric matrix offers enhanced mechanical stability, controlled drug release, and improved cellular adhesion and proliferation, leading to effective tissue regeneration. Infusing capsaicin/Zn-MCM-41 confers synergistic advantages, including accelerated wound closure, diminished inflammation, and enhanced tissue regeneration, culminating in superior wound healing outcomes. Comprehensive physicochemical characterization of the nanofiber was conducted, employing techniques such as EDS, EDX, XRD, FESEM, HRTEM, FTIR, BET, TGA, DSC and Zeta potential, confirming the successful synthesis of Zn/MCM-41 at the nanoscale, exhibiting uniform porosity, colloidal stability, and thermal resilience. In vivo quantitative assessment demonstrates a significant acceleration in wound healing facilitated by the composite nanofibers. Furthermore, the incorporation of capsaicin into Zn/MCM-41 augments the wound healing process, as corroborated by histological evaluations. In summary, our investigation introduces an advanced composite nanofiber formulation that promotes accelerated wound healing quantitatively through the synergistic amalgamation of PVA, PGA, capsaicin, and Zn/MCM-41. The demonstrated efficacy of the nanofibers underscores their potential in translational regenerative medicine and wound healing applications., 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.)

Colorectal cancer (CRC) is a significant health issue globally, affecting approximately 10 % of the world's population. The prevalence of CRC highlights the need for effective treatments and prevention strategies. The current therapeutic option, such as chemotherapy, has significant side effects. Thus, this study investigated the anticancer properties of Sanguinarine derivatives, an alkaloid found in traditional herbs via chemoinformatic approaches. Six Sanguinarine derivatives were discovered through virtual screening and molecular docking to determine their binding affinities against the mixed lineage kinase (MLK4) protein which is responsible for CRC. All the compounds were found to be more effective than standard drug used for colorectal cancer treatment, with Sanguinarine derivative 11 showing the highest affinity. The stability of the drug was confirmed through molecular dynamics simulations at 500 ns. This suggests that compound 11 has a higher chance of replacing 5-Fluorouracil, which is currently a widely used chemotherapy drug. Before molecular dynamics simulations, the pharmacokinetic and chemical properties of Sanguinarine derivatives were determined using pkCSM server and DFT method, respectively. The results support that compound 11 is a good drug candidate, as evidenced by Lipinski's Rule of Five. Therefore, compound 11 is recommended for further analysis via in vivo and in vitro studies to confirm its efficacy and safety., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: An imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms is believed to be a critical factor in the development of schizophrenia (SCZ) like neurological illnesses. Understanding the roles of ROS in the development of SCZ and the potential activity of natural antioxidants against SCZ could lead to more effective therapeutic options for the prevention and treatment of the illness., Methods: SCZ is a mental disorder characterised by progressive impairments in working memory, attention, and executive functioning. In present investigation, we summarized the experimental findings for understanding the role of oxidative stress (OS) in the development of SCZ and the potential neuroprotective effects of natural antioxidants in the treatment of SCZ., Results: Current study supports the use of the mentioned antioxidant natural compounds as a potential therapeutic candidates for the treatment of OS mediated neurodegeneration in SCZ., Discussion: Elevated levels of harmful ROS and reduced antioxidant defense mechanisms are indicative of increased oxidative stress (OS), which is associated with SCZ. Previous research has shown that individuals with SCZ, including non-medicated, medicated, first-episode, and chronic patients, exhibit decreased levels of total antioxidants and GSH. Additionally, they have reduced antioxidant enzyme levels such as catalase (CAT), glutathione (GPx), and, superoxide dismutase (SOD) and lower serum levels of brain-derived neurotrophic factor (BDNF) in their brain tissue. The mentioned natural antioxidants may assist in reducing oxidative damage in individuals with SCZ and increasing BDNF expression in the brain, potentially improving cognitive function and learning ability.

α-Glucosidase inhibitors are critical for diabetes management, with pyrazoles and thiazoles emerging as effective options. This research highlights curcumin-based pyrazole-thiazole hybrids as potential inhibitors, synthesizing derivatives and evaluating their inhibitory capabilities. The study involved the synthesis of novel compounds using hydrazonoyl halides, confirmed through elemental and spectral analyses. The synthesized derivatives exhibited significant α-glucosidase inhibition, with IC 50 values ranging from 3.37±0.25 to 16.35±0.37 μM. Among them, compound 7e demonstrated the strongest inhibition at 3.37±0.25 μM, outperforming the standard drug acarbose (IC 50 =5.36±0.31 μM). In silico assessments and molecular docking using AutoDock Vina revealed strong interactions, particularly with compounds 7b, 7e, 7f, and 7g, indicating their potential as stable and effective inhibitors. The results suggest that the synthesized pyrazole-thiazole hybrids hold promise as novel therapeutic agents for diabetes, warranting further exploration of their substituent effects for optimized inhibitor design., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Monoamine oxidase B (MAO-B) plays a pivotal role in the deamination process of monoamines, encompassing crucial neurotransmitters like dopamine and norepinephrine. The heightened interest in MAO-B inhibitors emerged after the revelation that this enzyme could potentially catalyze the formation of neurotoxic compounds from endogenous and exogenous sources. Computational screening methodologies serve as valuable tools in the quest for novel inhibitors, enhancing the efficiency of this pursuit. In this study, 43 acefylline derivatives were docked against the MAO-B enzyme for their chemotherapeutic potential and binding affinities that yielded GOLD fitness scores ranging from 33.21 to 75.22. Among them, five acefylline derivatives, namely, MAO-B14 , MAO-B15 , MAO-B16 , MAO-B20 , and MAO-B21 , displayed binding affinities comparable to the both standards istradefylline and safinamide. These derivatives exhibited hydrogen-bonding interactions with key amino acids Phe167 and Ile197/198, suggesting their strong potential as MAO-B inhibitors. Finally, molecular dynamics (MD) simulations were conducted to evaluate the stability of the examined acefylline derivatives over time. The simulations demonstrated that among the examined acefylline derivatives and standards, MAO-B21 stands out as the most stable candidate. Density functional theory (DFT) studies were also performed to optimize the geometries of the ligands, and molecular docking was conducted to predict the orientations of the ligands within the binding cavity of the protein and evaluate their molecular interactions. These results were also validated by simulation-based binding free energies via the molecular mechanics energies combined with generalized Born and surface area solvation (MM-GBSA) method. However, it is necessary to conduct in vitro and in vivo experiments to confirm and validate these findings in future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Irfan, Zahoor, Boulaamane, Javed, Hameed, Maurady, Muhammed, Ahmad, Al-Mutairi, Shahzadi, Al-Hussain and Zaki.)

Graphene-based nanomaterials have been proved to be robust sorbents for efficient removal of environmental contaminants including arsenic (As). Biobased graphene oxide (bGO-P) derived from sugarcane bagasse via pyrolysis, GO-C via chemical exfoliation, and magnetite nanoparticles (FeNPs) via green approach using Azadirachta indica leaf extract were synthesized and characterized by Ultraviolet-Visible Spectrophotometer (UV-vis.), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), mean particle size and Scanning electron microscopy (SEM) along with Energy dispersive spectroscopy (EDX) analysis. Compared to cellulose and hemicellulose, the lignin fraction was less in the precursor material. The GOC, bGO-P and FeNPs displayed maximum absorption at 230, 236, and 374 nm, respectively. FTIR spectrum showed different functional groups (C-OH, C-O-C, COOH and O-H) modifying the surfaces of synthesized materials. Graphene based nanomaterials showed clustered dense flakes of GO-C and thin transparent flakes of bGO-P. Elemental composition by EDX analysis of GO-C (71.26% C and 27.36% O), bGO-P (74.54% C and 24.61% O) and FeNPs (55.61% Fe, 4.1% C and 35.72% O) confirmed the presence of carbon, oxygen, and iron in synthesized nanomaterials. Sorption study was conducted with soil amended with different doses of synthesized nanomaterials (10, 50 and 250 mg) and exposed to 100, 300 and 500 ppm of As. Arsenic concentrations were estimated by colorimetry and atomic absorption spectroscopy (AAS). GO-C, bGO-P, and FeNPs showed substantial As removal efficiency i.e., 81 to 99.3%, 65 to 98.8% and 73.1-89.9%, respectively. Green synthesis of bGO-P and magnetite nanoparticles removed substantial amounts of As compared to GO-C and can be effectively deployed for As removal or immobilization. Higher and medium sorbent doses (250 and 50 mg) exhibited greater As removal and data was best fitted for Freundlich isotherm evidencing favorable sorption. Nevertheless, at low sorbent doses, data was best fitted for both models. Newly synthesized nanomaterials emerged as promising materials for As removal strategy for soil nano-remediation and can be effectively deployed in As contaminated soils., (© 2024. The Author(s).)

In this study, a simple in situ technique followed by hydrothermal method is used to synthesize a novel tremella-like structure of ZIF-67Co(OH)F@Co 3 O 4 /CC metal-organic framework (MOF) derived from zeolite imidazole. The in situ synthesis of metal-organic frameworks (MOFs) increases their conductivity and produces more active sites for ion insertion. Their unique, scalable design not only provides more space to accommodate volume change but also facilitates electrolyte penetration into the electrode resulting in more active materials being utilized and ion-electron transfer occurring faster during the cycle. As a result, the binder-free ZIF-67Co(OH)F@Co 3 O 4 /CC supercapacitor electrode exhibits typical pseudo-capacitance behaviour, with a specific capacitance of 442 F g -1 and excellent long-term cycling stability of 90% after 5000 cycles at 10 A g -1 ., 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., (This journal is © The Royal Society of Chemistry.)

The increase in antibiotic-resistant bacteria presents a significant risk to worldwide public health, emphasizing the necessity of novel approaches to address infections. Quorum sensing, an essential method of communication among bacteria, controls activities like the formation of biofilms, the production of virulence factors, and the synthesis of secondary metabolites according to the number of individuals in the population. Quorum quenching, which interferes with these processes, emerges as a vital approach to diminish bacterial virulence and prevent biofilm formation. Nanocarriers, characterized by their small size, high surface-area-to-volume ratio, and modifiable surface chemistry, offer a versatile platform for the disruption of bacterial communication by targeting various stages within the quorum sensing pathway. These features allow nanocarriers to infiltrate biofilms, disrupt cell membranes, and inhibit bacterial proliferation, presenting a promising alternative to traditional antibiotics. Integrating nanocarrier-based systems into combination therapies provides a multi-pronged approach to infection control, enhancing both the efficacy and specificity of treatment regimens. Nonetheless, challenges related to the stability, safety, and clinical effectiveness of nanomaterial-based antimicrobial treatments remain. Continued research and development are essential to overcoming these obstacles and fully harnessing the potential of nano-antimicrobial therapies. This review emphasizes the importance of quorum sensing in bacterial behavior and highlights the transformative potential of nanotechnology in advancing antimicrobial treatments, offering innovative solutions to combat antibiotic-resistant pathogens.

Global impact of viral diseases specially Monkeypox (mpox) and Marburg virus, emphasizing the urgent need for effective drug interventions. Oxymatrine is an alkaloid which has been selected and modified using various functional groups to enhance its efficacy. The modifications were evaluated using various computatioanal analysis such as pass prediction, molecular docking, ADMET, and molecular dynamic simulation. Mpox and Marburg virus were chosen as target diseases based on their maximum pass prediction spectrum against viral disease. After that, molecular docking, dynamic simulation, DFT, calculation and ADMET prediction were determined. The main objective of this study was to enhance the efficacy of oxymatrine derivatives through functional group modifications and computational analyses to develop effective drug candidates against mpox and Marburg viruses. The calculated binding affinities indicated strong interactions against both mpox virus and Marburg virus. After that, the molecular dynamic simulation was conducted at 100 ns, which confirmed the stability of the binding interactions between the modified oxymatrine derivatives and target proteins. Then, the modified oxymatrine derivatives conducted theoretical ADMET profiling, which demonstrated their potential for effective drug development. Moreover, HOMO-LUMO calculation was performed to understand the chemical reactivity and physicochemical properties of compounds. This computational analysis indicated that modified oxymatrine derivatives for the treatment of mpox and Marburg virus suggested effective drug candidates based on their binding affinity, drug-like properties, stability and chemical reactivity. However, further experimental validation is necessary to confirm their clinical value and efficacy as therapeutic candidates., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

This study investigated the adsorption of Oxytetracycline (OTC) from pharmaceutical wastewater using a kappa carrageenan based hydrogel (KPB). The aim of the present study was to explore the potential of KPB for long-term pharmaceutical wastewater treatment. A sustainable adsorbent was developed to address oxytetracycline (OTC) contamination. The hydrogel's structural and adsorption characteristics were examined using various techniques like Scanning Electron Microscope (SEM), Fourier Transform Infrared (FTIR), X-ray powder diffraction (XRD), and kinetic models. The results revealed considerable changes in the vibrational modes and adsorption bands of the hydrogel, suggesting the effective functionalization of Bentonite nano-clay. Kappa carrageenan based hydrogel achieved the maximum removal (98.5%) of OTC at concerntration of 40 mg/L, pH 8, cotact time of 140 min and adsorbent dose of 0.1 g (KPB-3). Adsorption of OTC increased up to 99% with increasing initial concentrations. The study achieved 95% adsorption capacity for OTC using a KPB film at a concentration of 20 mg/L and a 0.1 g adsorbent dose within 60 min. It also revealed that chemisorptions processes outperform physical adsorption. The Pseudo-Second-Order model, which emphasized the importance of chemical adsorption in the removal process, is better suited to represent the adsorption behavior. Excellent matches were found that R 2  = 0.99 for KPB-3, R 2  = 0.984 for KPB-2 and R 2  = 0.989 for KPB-1 indicated strong chemical bonding interactions. Statisctical analysis (ANOVA) was performed using SPSS (version 25) and it was found that pH and concentration had significant influence on OTC adsorption by the hydrogel, with p-values less than 0.05. The study identified that a Kappa carrageenan-based hydrogel with bentonite nano-clay and polyvinyl alcohol (PVA) can efficiently remove OTC from pharmaceutical effluent, with a p-value of 0.054, but weak positive linear associations with pH, temperature, and contact time. This research contributed to sustainable wastewater treatment and environmental engineering., (© 2024. The Author(s).)

Introduction: Toxic heavy metal pollution has been considered a major ecosystem pollution source. Unceasing or rare performance of Pb 2+ to the surrounding environment causes damage to the kidney, nervous, and liver systems. Microbial remediation has acquired prominence in recent decades due to its high efficiency, environment-friendliness, and cost-effectiveness., Methods: The lead biosorption by Bacillus subtilis was optimized by two successive paradigms, namely, a definitive screening design (DSD) and an artificial neural network (ANN), to maximize the sorption process., Results: Five physicochemical variables showed a significant influence ( p < 0.05) on the Pb 2+ biosorption with optimal levels of pH 6.1, temperature 30°C, glucose 1.5%, yeast extract 1.7%, and MgSO 4 .7H 2 O 0.2, resulting in a 96.12% removal rate. The Pb 2+ biosorption mechanism using B. subtilis biomass was investigated by performing several analyses before and after Pb 2+ biosorption. The maximum Pb 2+ biosorption capacity of B. subtilis was 61.8 mg/g at a 0.3 g biosorbent dose, pH 6.0, temperature 30°C, and contact time 60 min. Langmuir's isotherm and pseudo-second-order model with R 2 of 0.991 and 0.999 were suitable for the biosorption data, predicting a monolayer adsorption and chemisorption mechanism, respectively., Discussion: The outcome of the present research seems to be a first attempt to apply intelligence paradigms in the optimization of low-cost Pb 2+ biosorption using B. subtilis biomass, justifying their promising application for enhancing the removal efficiency of heavy metal ions using biosorbents from contaminated aqueous systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 El-Sharkawy, Khairy, Abbas, Zaki and El-Hadary.)

The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives 5a-5n and 7a-7n that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives 5a-5n and 7a-7n were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography-mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, 5j (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC 50 value of 5.16 ± 2.68 μM. This IC 50 value is notably lower than that of thiourea (23 ± 0.03 μM), indicating the significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akash, Rana, Aslam, Ahmad, Saif, Asghar, Sultan, Al-Hussain, Liaqat, Zaib and Zaki.)

Breast cancer (BC) is still one of the major issues in world health, especially for women, which necessitates innovative therapeutic strategies. In this study, we investigated the efficacy of retinoic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which plays a crucial role in the biosynthesis and metabolism of oestrogen and thereby influences the progression of BC and, the main objective of this investigation is to identify the possible drug candidate against BC through computational drug design approach including PASS prediction, molecular docking, ADMET profiling, molecular dynamics simulations (MD) and density functional theory (DFT) calculations. The result has reported that total eight derivatives with high binding affinity and promising pharmacokinetic properties among 115 derivatives. In particular, ligands 04 and 07 exhibited a higher binding affinity with values of -9.9 kcal/mol and -9.1 kcal/mol, respectively, than the standard drug epirubicin hydrochloride, which had a binding affinity of -8.2 kcal/mol. The stability of the ligand-protein complexes was further confirmed by MD simulations over a 100-ns trajectory, which included assessments of hydrogen bonds, root mean square deviation (RMSD), root mean square Fluctuation (RMSF), dynamic cross-correlation matric (DCCM) and principal component analysis. The study emphasizes the need for experimental validation to confirm the therapeutic utility of these compounds. This study enhances the computational search for new BC drugs and establishes a solid foundation for subsequent experimental and clinical research., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis, often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor-positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis-triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4-triazole structures, known for their potent aromatase inhibition and anti-cancer properties. These compounds were synthesized and characterized using 1 H-NMR, 13 C-NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF-7 breast cancer cell lines in vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors., Research Design and Methods: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed., Results: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%), piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors., Conclusions: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine, piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.

According to the World Health Organization, over 422 million people worldwide have diabetes, with the majority residing in low- and middle-income countries. Diabetes causes 1.5 million fatalities a year. The number of diabetes cases and its prevalence have progressively increased over the last few decades. This study aims to determine the phytochemicals in the edible part of Perkia javanica , predict their α-glucosidase inhibitory potential, one of the promising targets for diabetes, and then carry out in vitro and in vivo studies. The phytochemicals present in the n-butanol fraction of the methanol extract of P . javanica pods were analyzed using UHPLC-QTOF-MS/MS (Ultra-High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry). The UHPLC-QTOF analysis revealed the presence of 79 different compounds in the n-butanol fraction. Among these, six compounds demonstrated excellent binding affinities with α-glucosidase, surpassing the performance of two standard inhibitors, Miglitol and Voglibose. In vitro α-glucosidase inhibitory activities were assessed by the n-butanol fraction, followed by in vivo studies. According to the in vitro study, the inhibitory efficiency against α-glucosidase was determined to have an IC 50 value of 261.9 µg/mL. The in vivo findings revealed a significant reduction in blood glucose levels in Swiss albino mice treated with the same extract, decreasing from 462.66 mg/dL to 228.66 mg/dL. Additionally, the extract significantly increased the activity of the enzymes catalase and superoxide dismutase (SOD) and decreased the amount of malondialdehyde (MDA) in the liver and kidney tissue. The predicted physicochemical parameters indicated that most of the compounds would be excreted from the body after inhibition in the small intestine without being absorbed. Considering the low cost and wide availability of raw materials, P. javanica pods can serve as a good food supplement that may help prevent type 2 diabetes management.

Cardiovascular diseases, including heart failure, stroke, and hypertension, affect 608 million people worldwide and cause 32% of deaths. Combination therapy is required in 60% of patients, involving concurrent Renin-Angiotensin-Aldosterone-System (RAAS) and Neprilysin inhibition. This study introduces a novel multi-target in-silico modeling technique (mt-QSAR) to evaluate the inhibitory potential against Neprilysin and Angiotensin-converting enzymes. Using both linear (GA-LDA) and non-linear (RF) algorithms, mt-QSAR classification models were developed using 983 chemicals to predict inhibitory effects on Neprilysin and Angiotensin-converting enzymes. The Box-Jenkins method, feature selection method, and machine learning algorithms were employed to obtain the most predictive model with ~ 90% overall accuracy. Additionally, the study employed virtual screening of designed scaffolds (Chalcone and its analogues, 1,3-Thiazole, 1,3,4-Thiadiazole) applying developed mt-QSAR models and molecular docking. The identified virtual hits underwent successive filtration steps, incorporating assessments of drug-likeness, ADMET profiles, and synthetic accessibility tools. Finally, Molecular dynamic simulations were then used to identify and rank the most favourable compounds. The data acquired from this study may provide crucial direction for the identification of new multi-targeted cardiovascular inhibitors., (© 2024. The Author(s).)

Iron (Fe) is considered to be one of the most significant elements due to its wide applications. Recent years have witnessed a burgeoning interest in Fe catalysis as a sustainable and cost-effective alternative to noble metal catalysis in organic synthesis. The abundance and low toxicity of Fe, coupled with its competitive reactivity and selectivity, underscore its appeal for sustainable synthesis. A lot of catalytic reactions have been performed using heterogeneous catalysts of Fe oxide hybridized with support systems like aluminosilicates, clays, carbonized materials, metal oxides or polymeric matrices. This review provides a comprehensive overview of the latest advancements in Fe-catalyzed organic transformation reactions. Highlighted areas include cross-coupling reactions, C-H activation, asymmetric catalysis, and cascade processes, showcasing the versatility of Fe across a spectrum of synthetic methodologies. Emphasis is placed on mechanistic insights, elucidating the underlying principles governing iron-catalyzed reactions. Challenges and opportunities in the field are discussed, providing a roadmap for future research endeavors. Overall, this review illuminates the transformative potential of Fe catalysis in driving innovation and sustainability in organic chemistry, with implications for drug discovery, materials science, and beyond.

This study reports a novel CuSe-TiO 2 -GO composite, synthesized by a facile hydrothermal method at a controlled temperature, and investigates its electrochemical performance for supercapacitors (SCs) and photocatalytic behavior for degrading methylene blue (MB) dye. The compositional phase structure and chemical bond interaction were thoroughly investigated. The as-fabricated pristine, binary, and ternary composites underwent comprehensive characterization employing spectroscopic techniques and electrochemical analysis. Compared with pure and binary compounds (CuSe, TiO 2 , and binary CuSe-TiO 2 composites), the ternary CuSe-TiO 2 -GO composites demonstrated a high degradation efficiency while degrading MB in less than just 80 min (240 min, 100 min, and 140 min, respectively). The photocatalytic activity of the ternary CuSe-TiO 2 -GO composites is enhanced due to the highly positive conduction band of CuSe, leading to the quick excitation of electrons to the conduction band of CuSe. Subsequently, graphene oxide (GO) left holes on the photocatalyst surface for MB, as GO assisted the photoexcited electron-hole pairs, resulting in enhanced photocatalytic performance. The CuSe-TiO 2 -GO electrode for the supercapacitor indicates a 310.6 F/g and 135.2 F/g capacitance when the discharge current upsurges from 1 to 12 A/g. The good photocatalytic and energy storage performance is due to the smaller charge transfer resistance, which promotes efficient separation of electron-hole pairs.

A series of enantioenriched β-indolyl ketones as aromatase inhibitors (AI) is synthesized through the Michael-type Friedel-Crafts alkylation of indole. A highly efficient bifunctionalized amino catalyst is developed to access structurally diverse β-indolyl ketones in high yields (up to 91%) and excellent enantioselectivity (enantiomeric ratio up to 98:2). All the synthesized compounds demonstrated promising aromatase inhibitory potential, where ortho-substituted analogs (3c and 3e) were found most active with IC 50 values of 0.68 and 0.90 µM, respectively. Both of these compounds exhibited significant cytotoxicity (IC 50  = 0.34 and 0.37 µM) against the MCF-7 breast cancer cell line in the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Molecular docking studies of the synthesized compounds demonstrate favorable binding interactions with the estrogens controlling CYP19A1 (3EQM) and metabolizing CYP3A4 (5VCC) enzymes. Molecular dynamic (MD) simulation analysis revealed the essentiality of heme-ligand interactions to build a stable protein-ligand complex. An average root mean square deviation of 0.35 nm observed during a 100-ns MD simulation and binding free energy in the range of -190 to -227 kJ/mol calculated by g&#95;mmpbsa analysis authenticated the stability of the 3c-3EQM complex. ADMET and drug-likeness parameters supported the suitability of these indole derivatives as the drug lead to develop potent inhibitors for estrogen-dependent breast cancer., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

The current research focuses on the development of Ag-ZnO heterostructures through a "bottom-up" approach involving the assembly and extraction of Aloe barbadensis Miller gel. These heterostructures composed of metals/semiconductor oxide display distinct and notable optical, electrical, magnetic, and chemical properties that are not found in single constituents and also exhibit photocatalytic applications. These synthesized heterostructures were characterized by XRD, FTIR, SEM, and UV-visible spectroscopy. The high peak intensity of the Ag/ZnO composite shows the high crystallinity. The presence of Ag-O, Zn-O, and O-H bonding is verified using FTIR analysis. SEM analysis indicated the formation of spherical shapes of Ag/ZnO heterostructures. The Zn, O, and Ag elements are further confirmed by EDX analysis. Ag-ZnO heterostructures exhibited excellent photocatalytic activity and stability against the degradation of tubantin red 8BL dye under visible light irradiation., (© 2024. The Author(s).)

Calcium carbonate nanoparticles (CaCO 3 ) have been found to exhibit unique properties that show their potential to be used in various therapies. Green synthesis of CaCO 3 has been progressively gaining ac-ceptance due to its cost-effectiveness and energy-efficient nature. In the current study, different extracts of Ailanthus altissima were used to synthesize the calcium carbonate nanoparticles the synthesis and characterization of CCNPs were confirmed by using Fourier Transform Infra-Red spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The antioxidant activities (hydrogen peroxide, phosphomolydbenum, and ferric reducing) of calcium carbonate nanoparticles were affirmed by a good range of percentages of inhibition against free radical scavenging. The antidebate assays of CCNPs were observed by in-vitro and in silico approaches in a range at various concentrations while maximum inhibition occurred. In conclusion, the current study depicted that conjugated CaCO 3 with A. altissima has a good potential to cure oxidative stress and Type II diabetes and could be used in the future as biogenic nanomedicine for the treatment of other metabolic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Samad, Ejaz, Kousar, Al-Mutairi, Khalid, Amin, Bashir, Al-Hussain, Irfan and Zaki.)

Background: According to the International Diabetes Federation, there will be 578 million individuals worldwide with diabetes by 2030 and 700 million by 2045. One of the promising drug targets to fight diabetes is α-glucosidase (AG), and its inhibitors may be used to manage diabetes by reducing the breakdown of complex carbohydrates into simple sugars. The study aims to identify and validate potential AG inhibitors in natural sources to combat diabetes., Methods: Computational techniques such as structure-based virtual screening and molecular dyncamic simulation were employed to predict potential AG inhibitors from compounds of Oroxylum indicum . Finally, in silico results were validated by in vitro analysis using n -butanol fraction of crude methanol extracts., Results: The XP glide scores of top seven hits OI&#95;13, OI&#95;66, OI&#95;16, OI&#95;44, OI&#95;43, OI&#95;20, OI&#95;78 and acarbose were -14.261, -13.475, -13.074, -13.045, -12.978, -12.659, -12.354 and -12.296 kcal/mol, respectively. These hits demonstrated excellent binding affinity towards AG, surpassing the known AG inhibitor acarbose. The MM-GBSA dG binding energies of OI&#95;13, OI&#95;66, and acarbose were -69.093, -62.950, and -53.055 kcal/mol, respectively. Most of the top hits were glycosides, indicating that active compounds lie in the n -butanol fraction of the extract. The IC 50 value for AG inhibition by n -butanol fraction was 248.1 μg/ml, and for that of pure acarbose it was 89.16 μg/ml. The predicted oral absorption rate in humans for the top seven hits was low like acarbose, which favors the use of these compounds as anti-diabetes in the small intestine., Conclusion: In summary, the study provides promising insights into the use of natural compounds derived from O. indicum as potential AG inhibitors to manage diabetes. However, further research, including clinical trials and pharmacological studies, would be necessary to validate their efficacy and safety before clinical use., 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., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

The rise of drug resistance in Plasmodium falciparum, rendering current treatments ineffective, has hindered efforts to eliminate malaria. To address this issue, the study employed a combination of Systems Biology approach and a structure-based pharmacophore method to identify a target against P. falciparum. Through text mining, 448 genes were extracted, and it was discovered that plasmepsins, found in the Plasmodium genus, play a crucial role in the parasite's survival. The metabolic pathways of these proteins were determined using the PlasmoDB genomic database and recreated using CellDesigner 4.4.2. To identify a potent target, Plasmepsin V (PF13&#95;0133) was selected and examined for protein-protein interactions (PPIs) using the STRING Database. Topological analysis and global-based methods identified PF13&#95;0133 as having the highest centrality. Moreover, the static protein knockout PPIs demonstrated the essentiality of PF13&#95;0133 in the modeled network. Due to the unavailability of the protein's crystal structure, it was modeled and subjected to a molecular dynamics simulation study. The structure-based pharmacophore modeling utilized the modeled PF13&#95;0133 (PfPMV), generating 10 pharmacophore hypotheses with a library of active and inactive compounds against PfPMV. Through virtual screening, two potential candidates, hesperidin and rutin, were identified as potential drugs which may be repurposed as potential anti-malarial agents., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity., 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., (© 2024 The Authors.)

Benzofurans have intrigued both pharmaceutical researchers and chemists owing to the medicinal usage of their derivatives against copious disease-causing agents (i.e., bacteria, viruses, and tumors). These heterocyclic scaffolds are pervasively encountered in a number of natural products and drugs. The ever-increasing utilization of benzofuran derivatives as pharmaceutical agents persuaded the chemists to devise novel and facile methodological approaches to assemble the biologically potent benzofuran nucleus. This review summarizes the current developments regarding the innovative synthetic routes and catalytic strategies to procure the synthesis of benzofuran heterocycles with their corresponding mechanistic details, reported by several research groups during 2021-2023., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Gastric cancer is considered a class 1 carcinogen that is closely linked to infection with Helicobacter pylori (H. pylori), which affects over 1 million people each year. However, the major challenge to fight against H. pylori and its associated gastric cancer due to drug resistance. This research gap had led our research team to investigate a potential drug candidate targeting the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. In this study, a total of 45 daidzein derivatives were investigated and the best 10 molecules were comprehensively investigated using in silico approaches for drug development, namely pass prediction, quantum calculations, molecular docking, molecular dynamics simulations, Lipinski rule evaluation, and prediction of pharmacokinetics. The molecular docking study was performed to evaluate the binding affinity between the target protein and the ligands. In addition, the stability of ligand-protein complexes was investigated by molecular dynamics simulations. Various parameters were analysed, including root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM). The results has confirmed that the ligand-protein complex CID: 129661094 (07) and 129664277 (08) formed stable interactions with the target protein. It was also found that CID: 129661094 (07) has greater hydrogen bond occupancy and stability, while the ligand-protein complex CID 129664277 (08) has greater conformational flexibility. Principal component analysis revealed that the ligand-protein complex CID: 129661094 (07) is more compact and stable. Hydrogen bond analysis revealed favourable interactions with the reported amino acid residues. Overall, this study suggests that daidzein derivatives in particular show promise as potential inhibitors of H. pylori., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Single-point mutations in the Kirsten rat sarcoma (KRAS) viral proto-oncogene are the most common cause of human cancer. In humans, oncogenic KRAS mutations are responsible for about 30% of lung, pancreatic, and colon cancers. One of the predominant mutant KRAS G12D variants is responsible for pancreatic cancer and is an attractive drug target. At the time of writing, no Food and Drug Administration (FDA) approved drugs are available for the KRAS G12D mutant. So, there is a need to develop an effective drug for KRAS G12D. The process of finding new drugs is expensive and time-consuming. On the other hand, in silico drug designing methodologies are cost-effective and less time-consuming. Herein, we employed machine learning algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF) for the identification of new inhibitors against the KRAS G12D mutant. A total of 82 hits were predicted as active against the KRAS G12D mutant. The active hits were docked into the active site of the KRAS G12D mutant. Furthermore, to evaluate the stability of the compounds with a good docking score, the top two complexes and the standard complex (MRTX-1133) were subjected to 200 ns MD simulation. The top two hits revealed high stability as compared to the standard compound. The binding energy of the top two hits was good as compared to the standard compound. Our identified hits have the potential to inhibit the KRAS G12D mutation and can help combat cancer. To the best of our knowledge, this is the first study in which machine-learning-based virtual screening, molecular docking, and molecular dynamics simulation were carried out for the identification of new promising inhibitors for the KRAS G12D mutant.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC 50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC 50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis , respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Saeed, Shahzadi, Zahoor, Al-Mutairi, Kamal, Faisal, Irfan, Al-Hussain, Muhammed and Zaki.)

4-Acetylpyridine 1 and malononitrile 2 were allowed to react in a 3MCRs with dimedone 3a or cyclohexa-1,3-dione 3b under reflux to afford 4-methyl-4-(pyridin-4-yl)-5,6,7,8-tetrahydro-4 H -chromene derivatives 4a,b respectively. The mechanism of the reaction has been studied and the structures elucidated by analytical, spectral as well as X-ray crystallographic data. Heterocyclic compounds find widespread application in pharmaceutical and agrochemical products. Docking analyses were performed on the synthesized compounds to assess their binding modes with various amino acids of the target protein tubulin (PDB Code - 1SA0). The results indicated promising binding scores for compounds 4a and 4b , suggesting a strong affinity for the tubulin binding site. Finally, ADMET for the synthesized compounds 4a, 4b, 5, 8a and 8b were carried out. The drug likeness and pharmacokinetic properties of the prepared compounds were also evaluated. Notably, all of the novel compounds adhered to Lipinski's rule (Ro5) without any violations., 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., (© 2024 The Authors.)

The pancreas is a heterocrine gland that has both exocrine and endocrine parts. Most pancreatic cancer begins in the cells that line the ducts of the pancreas and is called pancreatic ductal adenocarcinoma (PDAC). PDAC is the most encountered pancreatic cancer type. One of the most important characteristic features of PDAC is neuropathy which is primarily due to perineural invasion (PNI). PNI develops tumor microenvironment which includes overexpression of fibroblasts cells, macrophages, as well as angiogenesis which can be responsible for neuropathy pain. In tumor microenvironment inactive fibroblasts are converted into an active form that is cancer-associated fibroblasts (CAFs). Neurotrophins they also increase the level of Substance P, calcitonin gene-related peptide which is also involved in pain. Matrix metalloproteases are the zinc-associated proteases enzymes which activates proinflammatory interleukin-1β into its activated form and are responsible for release and activation of Substance P which is responsible for neuropathic pain by transmitting pain signal via dorsal root ganglion. All the molecules and their role in being responsible for neuropathic pain are described below., (© 2024 Wiley Periodicals LLC.)

Cancer, a life-disturbing and lethal disease with a high global impact, causes significant economic, social, and health challenges. Breast cancer refers to the abnormal growth of cells originating from breast tissues. Hormone-dependent forms of breast cancer, such as those influenced by estrogen, prompt the exploration of estrogen receptors as targets for potential therapeutic interventions. In this study, we conducted e-QSAR molecular docking and molecular dynamics analyses on a diverse set of inhibitors targeting estrogen receptor alpha (ER-α). The e-QSAR model is based on a genetic algorithm combined with multilinear regression analysis. The newly developed model possesses a balance between predictive accuracy and mechanistic insights adhering to the OECD guidelines. The e-QSAR model pointed out that sp 2 -hybridized carbon and nitrogen atoms are important atoms governing binding profiles. In addition, a specific combination of H-bond donors and acceptors with carbon, nitrogen, and ring sulfur atoms also plays a crucial role. The results are supported by molecular docking, MD simulations, and X-ray-resolved structures. The novel results could be useful for future drug development for ER-α., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aim: In this study, a neoteric and expedient oxidation method is applied for a variety of Hantzsch 1,4-dihydropyridine derivatives such as 1,4-dihydro- 2,6-dimethyl-3,5-diacetylpyridine, 3,5-bis-hydrazono--2,6-dimethyl-1,4-dihydropyridine, and 3,5-bis-thiazoly-2,6-dimethyl-1,4-dihydro pyridine., Method: This simple oxidation is based upon the in situ generation of nitrous acid from an aqueous sodium nitrite and acetic acid mixture and could be used to downgrade costs, sustain resources, and minimize chemical wastes. Also, a molecular modeling strategy was used to study the mechanism of action for various derivatives of bis-hydrazinylidene- thiazole as the protein Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor through evaluating their binding scores and modes compared with Sorafenib as a reference standard., Result: The results revealed that the interaction of hydrazinylidene and thiazole as an anticancer Tyrosine Kinase inhibitor has been improved., Conclusion: Additionally, the compounds exhibiting the highest activity were assessed for their potential anticancer effects against HepG-2, MCF-7, and WI-38 cells, and the outcomes demonstrated encouraging activity against cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1 H NMR, 13 C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Corrosion is a major problem that can lead to the degradation of metal structures. In this study, we developed a novel corrosion-protective coating for metal substrates based on a modified epoxy acrylate formulation reinforced with halloysite nanotubes (HNTs). Epoxy acrylate oligomers were first synthesized through the acrylation of epoxy using acrylic acid, followed by copolymerization with butyl methacrylate/vinyl acetate monomers to produce grafted epoxy acrylates (GEA). HNTs were then incorporated into the polymeric dispersion at weight loadings of 1%, 1.5%, and 2%. The corrosion resistance and waterproofing properties of the coatings were evaluated. The results showed that steel samples coated with HNTs-modified GEA showed no signs of rusting even after 16 days of immersion in a corrosive solution, whereas those coated with GEA alone showed rusting after only 9 days. These results demonstrate the effectiveness of HNTs-modified GEA coatings in protecting steel surfaces against corrosion. The coatings are also water-resistant and can be easily applied. This work provides a new approach to developing corrosion-protective coatings for metal substrates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Asif, Ahmad, Saif, Anjum and Zaki.)

Due to the high rates of drug development failure and the massive expenses associated with drug discovery, repurposing existing drugs has become more popular. As a result, we have used QSAR modelling on a large and varied dataset of 657 compounds in an effort to discover both explicit and subtle structural features requisite for ACE2 inhibitory activity, with the goal of identifying novel hit molecules. The QSAR modelling yielded a statistically robust QSAR model with high predictivity (R 2 tr =0.84, R 2 ex =0.79), previously undisclosed features, and novel mechanistic interpretations. The developed QSAR model predicted the ACE2 inhibitory activity ( P IC 50 ) of 1615 ZINC FDA compounds. This led to the detection of a P IC 50 of 8.604 M for the hit molecule (ZINC000027990463). The hit molecule's docking score is -9.67 kcal/mol (RMSD 1.4). The hit molecule revealed 25 interactions with the residue ASP40, which defines the N and C termini of the ectodomain of ACE2. The HIT molecule conducted more than thirty contacts with water molecules and exhibited polar interaction with the ARG522 residue coupled with the second chloride ion, which is 10.4 nm away from the zinc ion. Both molecular docking and QSAR produced comparable findings. Moreover, MD simulation and MMGBSA studies verified docking analysis. The MD simulation showed that the hit molecule-ACE2 receptor complex is stable for 400 ns, suggesting that repurposed hit molecule 3 is a viable ACE2 inhibitor.

Cardiovascular diseases (CVD) such as heart failure, stroke, and hypertension affect 64.3 million people worldwide and are responsible for 30% of all deaths. Primary inhibition of the angiotensin-converting enzyme (ACE) is significant in the management of CVD. In the present study, the genetic algorithm-multiple linear regressions (GA-MLR) method is used to generate highly predictive and statistically significant ( R 2 = 0.70-0.75, Q 2 LOO =0.67-0.73, Q 2 LMO =0.66-0.72, CCC ex =0.70-0.78) quantitative structure-activity relationships (QSAR) models conferring to OECD requirements using a dataset of 255 structurally diverse and experimentally validated ACE inhibitors. The models contain simply illustratable Padel, Estate, and PyDescriptors that correlate structural scaffold requisite for ACE inhibition. Also, constraint-based molecular docking reveals an interaction profile between ligands and enzymes which is then correlated with the essential structural features associated with the QSAR models. The QSAR-based virtual screening was utilized to find novel lead molecules from a designed database of 102 thiadiazole derivatives. The Applicability domain (AD), Molecular Docking, Molecular dynamics, and ADMET analysis suggest two compound D24 and D40 are inflexibly linked to the protein binding site and follows drug-likeness properties.Communicated by Ramaswamy H. Sarma.

Epidermal growth factor receptor (EGFR) tyrosine kinases are overexpressed in several human cancers and could serve as a promising anti-cancer drug target. With this in view, the main aim of the present study was to identify spices having the potential to inhibit EGFR tyrosine kinase. The structure-based virtual screening of spice database consisting of 1439 compounds with EGFR tyrosine kinase (PDB ID: 3W32) was carried out using Glide. Top scored 18 hits (XP Glide Score ≥ -10.0 kcal/mol) was further docked with three EGFR tyrosine kinases and three EGFR T790M/L858R mutants using AutodockVina, followed by ADME filtration. The best three hits were further refined by Molecular Dynamics (MD) simulation and MM-GBSA-based binding energy calculation. The overall docking results of the selected hits with both EGFR and EGFR T790M/L858R were quite satisfactory and showed strong binding compared to the three coligands. Detailed MD analysis of CL&#95;07, AC&#95;11 and AS&#95;49 also showed the stability of the protein-ligand complexes. Moreover, the hits were drug-like, and MM-GBSA binding free energy of CL&#95;07 and AS&#95;49 was established to be far better. AC&#95;11 was found to be similar to the known inhibitor Gefitinib. Most of the potential hits are available in Allium cepa , CL&#95;07 and AS&#95;49 available in Curcuma longa and Allium sativum , respectively. Therefore, these three spices could be used as a potential therapeutic candidate against cancer caused by overexpression of EGFR after validation of the observations of this study in in-vitro experiments. Further extensive work is needed to improve the scaffolds CL&#95;07, AC&#95;11, AC&#95;17, and AS&#95;49 as potential anti-cancer drugs.Communicated by Ramaswamy H. Sarma.

Biomaterials play a vital role in targeting therapeutics. Over the years, several biomaterials have gained wide attention in the treatment and diagnosis of diseases. Scientists are trying to make more personalized treatments for different diseases, as well as discovering novel single agents that can be used for prognosis, medication administration, and keeping track of how a treatment works. Theranostics based on nano-biomaterials have higher sensitivity and specificity for disease management than conventional techniques. This review provides a concise overview of various biomaterials, including carbon-based materials like fullerenes, graphene, carbon nanotubes (CNTs), and carbon nanofibers, and their involvement in theranostics of different diseases. In addition, the involvement of imaging techniques for theranostics applications was overviewed. Theranostics is an emerging strategy that has great potential for enhancing the accuracy and efficacy of medicinal interventions. Despite the presence of obstacles such as disease heterogeneity, toxicity, reproducibility, uniformity, upscaling production, and regulatory hurdles, the field of medical research and development has great promise due to its ability to provide patients with personalised care, facilitate early identification, and enable focused treatment., (© 2024. The Author(s).)

A lysine-specific demethylase is an enzyme that selectively eliminates methyl groups from lysine residues. KDM5A, also known as JARID1A or RBP2, belongs to the KDM5 Jumonji histone demethylase subfamily. To identify novel molecules that interact with the LSD5A receptor, we created a quantitative structure-activity relationship (QSAR) model. A group of 435 compounds was used in a study of the quantitative relationship between structure and activity to guess the IC50 values for blocking LASD5A. We used a genetic algorithm-multilinear regression-based quantitative structure-activity connection model to forecast the bioactivity ( P IC 50 ) of 1615 food and drug administration pharmaceuticals from the zinc database with the goal of repurposing clinically used medications. We used molecular docking, molecular dynamic simulation modelling, and molecular mechanics generalised surface area analysis to investigate the molecule's binding mechanism. A genetic algorithm and multi-linear regression method were used to make six variable-based quantitative structure-activity relationship models that worked well ( R 2 = 0.8521, Q 2 LOO = 0.8438, and Q 2 LMO = 0.8414). ZINC000000538621 was found to be a new hit against LSD5A after a quantitative structure-activity relationship-based virtual screening of 1615 zinc food and drug administration compounds. The docking analysis revealed that the hit molecule 11 in the KDM5A binding pocket adopted a conformation similar to the pdb-6bh1 ligand (docking score: -8.61 kcal/mol). The results from molecular docking and the quantitative structure-activity relationship were complementary and consistent. The most active lead molecule 11, which has shown encouraging results, has good absorption, distribution, metabolism, and excretion (ADME) properties, and its toxicity has been shown to be minimal. In addition, the MTT assay of ZINC000000538621 with MCF-7 cell lines backs up the in silico studies. We used molecular mechanics generalise borne surface area analysis and a 200-ns molecular dynamics simulation to find structural motifs for KDM5A enzyme interactions. Thus, our strategy will likely expand food and drug administration molecule repurposing research to find better anticancer drugs and therapies.Communicated by Ramaswamy H. Sarma.

A series of novel thieno[2,3- b ]pyridines linked to N -aryl carboxamides or (carbonylphenoxy)- N -(aryl)acetamides, as well as bis(thieno[2,3- b ]pyridines) linked to piperazine core via methanone or carbonylphenoxyethanone units, were synthesized by treating the appropriate chloroacetyl- or bis-bromoacetyl derivatives with 2-mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. The spectral data were used to determine the compositions of novel compounds., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The elimination of hazardous industrial pollutants from aqueous solutions is an emerging area of scientific research and a worldwide problem. An efficient catalyst, Ag-CuO was synthesized for the degradation of methylene blue, the chemical sensing of ammonia. A simple novel synthetic method was reported in which new plant material Capparis decidua was used for the reduction and stabilization of the synthesized nanocatalyst. A Varying amount of Ag was doped into CuO to optimize the best catalyst that met the required objectives. Through this, the Ag-CuO nanocomposite was characterized by XRD, SEM, HR-TEM, EDX, and FTIR techniques. The mechanism of increased catalytic activity with Ag doping involves the formation of charge sink and suppression of drop back probability of charge from conduction to valance band. Herein, 2.7 mol % Ag-CuO exhibited better catalytic activities and it was used through subsequent catalytic experiments. The experimental conditions such as pH, catalyst dose, analyte initial concentration, and contact time were optimized. The as-synthesized nanocomposite demonstrates an excellent degradation efficacy of MB which is 97% at pH 9. More interestingly, the as-synthesized catalyst was successfully applied for the chemical sensing of ammonia even at very low concentrations. The lower limit of detection (LLOD) also called analytic sensitivity was calculated for ammonia sensing and found to be 1.37 ppm., (© 2024. The Author(s).)

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R2 = 0.800-793, Q2LOO = 0.734-0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit's docking score (-8.208 kcal/mol) and PIC50 (7.85 M) demonstrated a significant affinity for SARS-CoV-2's main protease. Based on post-covid neurodegenerative episodes in Alzheimer's and Parkinson's-like disorders and MAO-B's role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2's primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR's COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zaki 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.)

The remediation of pesticides from the environment is one of the most important technology nowadays. Herein, magnesium oxide (MgO) nanoparticles and calcium-doped magnesium oxide (Ca-doped MgO) nanoparticles were synthesized by the co-precipitation method and were used for the degradation of thiamethoxam pesticide in aqueous media. Characterization of the MgO and Ca-doped MgO nanoparticles were performed by XRD, SEM, EDX, and FT-IR analysis to verify the synthesis and variations in chemical composition. The band gap energy and crystalline size of MgO and Ca-doped MgO nanoparticles were found to be 4.8 and 4.7 eV and 33 and 34 nm respectively. The degradation of thiamethoxam was accomplished regarding the impact of catalyst dosage, contact time, temperature, pH, and initial pesticide concentration. The pH study indicates that degradation of thiamethoxam depends on pH and maximum degradation (66%) was obtained at pH 5 using MgO nanoparticles. In contrast, maximum degradation (80%) of thiamethoxam was observed at pH 8 employing Ca-doped MgO nanoparticles. The percentage degradation of thiamethoxam was initially increasing but decreased at higher doses of the catalysts. The degradation of the pesticide was observed to be increased with an increase in contact time while high at room temperature but decreased with a temperature rise. The effect of the initial concertation of pesticide indicates that degradation of pesticide increases at low concentrations but declines at higher concentrations. This research study reveals that doping of MgO nanoparticles with calcium enhanced the degradation of thiamethoxam pesticide in aqueous media., (© 2024. The Author(s).)