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Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a-t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC 50 value of the inhibitors (15.78 μM) is lower than that of kojic acid (17.3 μM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC 50 value of 3.5 ± 1.2  μM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally., Method: Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses. in vitro and in silico techniques were used in the current study to identify novel inhibitors of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles against the SARS-CoV-2 spike protein., Result: Interestingly, all the tested molecules demonstrated substantial inhibition of spike protein with 91.81-57.90% inhibition. The spike protein was remarkably inhibited by compounds 6k (91.83%), 6j (89.75%), 6m (87.69%),6i (86.60%), 6l (85.40%), 6h (84.70%), 6l (84.70%), 6g (83.40%), 6b (82.60%), 6f (81.90%), while compounds 6d 6a, 6c, and 6e exhibited significant activity against spike protein with 79.60%, 77.10%, 75.30%, and 57.90% inhibition, respectively. The binding mechanism of these novel inhibitors with spike protein was deduced in silico, which reflects that the active molecules firmly bind with the receptor binding domain (RBD) of spike protein, thereby inhibiting its function., Conclusion: The combined in vitro and in silico investigations unfold the therapeutic potential of coumarin-thiazolotriazole scaffolds in the treatment of SARS-CoV-2 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 μM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase ( K i = 3.96 ± 0.0048 μM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

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.)

Shigellosis, induced by Shigella flexneri, constitutes a significant health burden in developing nations, particularly impacting socioeconomically disadvantaged communities. Designated as the second most prevalent cause of diarrheal illness by the World Health Organization (WHO), it precipitates an estimated 212,000 fatalities annually. Within the spectrum of S. flexneri strains, serotype X is notably pervasive and resilient, yet its comprehensive characterization remains deficient. The present investigation endeavors to discern potential pharmacological targets and repurpose existing drug compounds against S. flexneri serotype X. Employing the framework of subtractive genomics, the study interrogates the reference genome of S. flexneri Serotype X (strain 2,002,017; UP000001884) to delineate its proteome into categories of non-homologous, non-paralogous, essential, virulent, and resistant constituents, thereby facilitating the identification of therapeutic targets. Subsequently, a screening of approximately 9000 compounds from the FDA library against the identified drug target aims to delineate efficacious agents for combating S. flexneri serotype X infections. The application of subtractive genomics methodology yields prognostic insights, unveiling non-paralogous proteins (n = 4122), non-homologues (n = 1803), essential (n = 1246), drug-like (n = 389), resistant (n = 167), alongside 42 virulent proteins within the reference proteome. This iterative process culminates in the identification of Serine O-acetyltransferase as a viable drug target. Subsequent virtual screening endeavors to unearth FDA-approved medicinal compounds capable of inhibiting Serine O-acetyltransferase. Noteworthy candidates such as DB12983, DB15085, DB16098, DB16185, and DB16262 emerge, exhibiting potential for mitigating S. flexneri Serotype X. Despite the auspicious findings, diligent scrutiny is imperative to ascertain the efficacy and safety profile of the proposed drug candidates vis-à-vis S. flexneri., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a chronic disorder and still a challenge throughout the world, and therefore the search for safe and effective inhibitors for α-amylase and α - glucosidase is increasing day by day. In this work, we try to carry out the synthesis, modification, and computer-aided results of and biological research on thiadiazole-based Schiff base derivatives and evaluate their in vitro α-amylase and α - glucosidase inhibitory potential ( 1 - 15 ). In the current series, all of the synthesized analogues were shown to have potential inhibitory effects on targeted enzymes. The IC 50 values for α-amylase values ranged from 20.10 ± 0.40 to 0.80 ± 0.05 μM, compared with the standard drug acarbose having an IC 50 value of 10.30 ± 0.20 μM, while for α-glucosidase, the IC 50 values ranged from 20.10 ± 0.50 to 1.20 ± 0.10 μM, compared to acarbose with an IC 50 value of 9.80 ± 0.20 μM. For better understanding, a SAR investigation was undertaken. In this series, nine scaffolds ( 1 , 2 , 3 , 6 , 9 , 10 , 11 , 13 , and 15 ) were more active than the reference drug and the docking parameter RMSD values for α-glucosidase and α-amylase were 1.766, 2.7746, 1.6025, 2.2112, 3.5860, 2.3360, 1.6178, 2.0254, and 2.0797 and 2.6020, 1.9509, 3.1642, 1.7547, 2.2130, 1.4221, and 1.1087, respectively. The toxicity of the selected analogues was calculated by using the OSIRIS tool, and the TPSA values were found to be lower than 140 to represent the drug-like properties; those from Molinspiration were studied as well. The following properties were studied and found to have better biological properties. The remaining analogues ( 4 , 5 , 7 , 8 , 12 , and 14 ) were also identified as potential inhibitors of both enzymes, but they were less active than the reference due to the substituents attached to the aromatic parts. The structures of synthesized compounds were confirmed through different spectroscopic analyses., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC 50 value of 0.294 μM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC 50 value of 0.519 μM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In this work, Schiff bases and Thiazolidin-4-ones, were synthesized using Sonication and Microwave techniques, respectively. The Schiff base derivatives ( 3a-b ) were synthesized via the reaction of Sulfathiazole ( 1 ) with benzaldehyde derivatives ( 2a-b ), followed by the synthesis of 4-thiazoledinone ( 4a-b ) derivatives by cyclizing the synthesized Schiff bases through thioglycholic acid. All the synthesized compounds were characterized by spectroscopic techniques such as FT IR, NMR and HRMS. The synthesized compounds were tested for their in vitro antimicrobial and antioxidant and in vivo cytotoxicity and hemolysis ability. The synthesized compounds displayed better antimicrobial and antioxidant activity and low toxicity in comparison to reference drugs and negative controls, respectively. The hemolysis test revealed the compounds exhibit lower hemolytic effects and hemolytic values are comparatively low and the safety of compounds is in comparison with standard drugs. Theoretical calculations were carried out by using the molecular operating environment (MOE) and Gaussian computing software and observations were in good agreement with the in vitro and in vivo biological activities. Petra/Osiris/Molinspiration (POM) results indicate the presence of three combined antibacterial, antiviral and antitumor pharmacophore sites. The molecular docking revealed the significant binding affinities and non-bonding interactions between the compounds and Erwinia Chrysanthemi (PDB ID: 1SHK). The molecular dynamics simulation under in silico physiological conditions revealed a stable conformation and binding pattern in a stimulating environment. HighlightsNew series of Thaiazolidin-4-one derivatives have been synthesized.Sonication and microwave techniques are used.Antimicrobial, Antioxidant, cytotoxicity, and hemolysis activities were observed for all synthesized compounds.Molecular Docking and DFT/POM analyses have been predicted.Communicated by Ramaswamy H. Sarma.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series ( 1 - 12 ), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC 50 values of 18.10 ± 0.20 to 1.10 ± 0.10 μM. In this series, analogues 4 , 8 , and 9 show remarkable inhibition profile IC 50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 μM by using acarbose as a standard, whose IC 50 is 11.50 ± 0.30 μM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives. Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield 3 , 4 , 8 , 11 , 14 , 16, 19, 20, 21, 22 and 23 . Compounds 8, 11, 16, 20 and 23 are investigated against OVCAR-3 and HeLa, using LLC-MK2 and cis -Pt as references. in silico and spectral studies were analyzed for the selected compounds. Results: Compounds 20 and 23 at 100 ns were the most potent compounds, so molecular dynamics studies were performed. Conclusion: Compound 23 was the most active toward the HeLa cervical cell line, and compound 20 was the most active toward the Ovcar-3 cell line.

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis-benzimidazole derivatives (1-25) by using 3,3'-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1 HNMR, 13 CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (hCA-IX) was evaluated in-vitro, where several synthesized derivatives showed potent inhibition of hCA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3-5, 7-8, 13-16, 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50  = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents., 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.)

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).)

Zingiber officinale and Citrus limon , well known as ginger and lemon, are two vegetals widely used in traditional medicine and the culinary field. The juices of the two vegetals were evaluated based on their inflammation, both in vivo and in vitro. High-performance liquid chromatography (HPLC) was used to characterize different juices from Zingiber officinale Roscoe and Citrus limon . After the application of the HPLC method, different compounds were identified, such as 6-gingerol and 6-gingediol from the ginger juice and isorhamnetin and hesperidin from the lemon juice. In addition, the two juices and their formulation were assessed for their anti-inflammatory activity, in vitro by utilizing the BSA denaturation test, in vivo using the carrageenan-induced inflammation test, and the vascular permeability test. Important and statistically significant anti-inflammatory activities were observed for all juices, especially the formulation. The results of our work showed clearly that the Zingiber officinale and Citrus limon juices protect in vivo the development of the rat paw edema, especially the formulation F composed of the Zingiber officinale and Citrus limon juices, which shows an anti-inflammatory activity equal to -35.95% and -44.05% using 10 and 20 mg/kg of the dose, respectively. Our work also showed that the formulation was the most effective tested extract since it inhibits the vascular permeability by -37% and -44% at the doses of 200 and 400 mg/kg, respectively, and in vitro via the inhibition of the denaturation of BSA by giving a synergetic effect with the highest IC 50 equal to 684.61 ± 7.62 μg/mL corresponding to the formulation F. This work aims to develop nutraceutical preparations in the future and furnishes the support for a new investigation into the activities of the various compounds found in Zingiber officinale Roscoe and Citrus limon ., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Benzimidazoles are classified as a category of heterocyclic compounds. Molecules having benzimidazole motifs show promising utility in organic and scientific studies. A series of mono-substituted benzimidazoles were synthesized by ZnO-NPs via cyclocondensation between substituted aromatic aldehydes and o -phenylene diamine. The synthesized compounds were characterized and compared with the traditional methods. The nano-catalyzed method displayed a higher yield, shorter time and recyclable catalyst. The DFT study and antioxidant activity were investigated for benzo[ d ]imidazole derivatives. Compound 2a exhibited the highest antioxidant activity among the tested compounds. We focused on the catalytic activity of ZnO in the synthesis of heterocyclic structures with the goal of stimulating further progress in this field. The superiorities of this procedure are high yield of product, low amounts of catalyst and short reaction time.

Schiff bases are mentioned as strongly important molecular scaffolds of industrial and medicinal purposes. Due to wide range applications of carbazate derivatives herein synthesis and characterization of a new Schiff base ligand, ( E )-ethyl 2 -( 4 -methoxybenzylidene)hydrazinecarboxylate and 4-( nitrobenzaldehyde)ethylcarbazate are reported. The compound was characterized on the basis of experimental and density functional theory calculations (using the B3LYP and 6-31 G(d,p)formalism combination). Among characterization techniques elemental analysis, FT-IR, UV-Vis and NMR spectroscopic evaluations were mainly employed to carry out the formulation of the compound. In addition to computational validation of characterization other significant molecular parameters were also evaluated including geometry optimization, frontier molecular orbital analysis (FMO) and Columbic interaction of different constituent atoms of the title compound. A good agreement has been found between DFT and experimental outcomes confined to prove the structure of the compound. Moreover, molecular docking and antimicrobial studies have proven the Schiff base as an effective bioactive compound.Communicated by Ramaswamy H. Sarma.

Bilophila wadsworthia is one of the prominent sources of hydrogen sulfide (H 2 S) production in appendices, excessive levels of which can result in a weaker colonic mucus barrier, inflammatory bowel disease, and colorectal cancer. Isethionate sulfite-lyase (IslA) enzyme catalyzes H 2 S production by cleaving CS bond in isethionate, producing acetaldehyde and sulfite. In this study, we aimed to identify potential substrate antagonists for IsIA using a structure-based drug design. Initially, pharmacophore-based computational screening of the ZINC20 database yielded 66 hits that were subjected to molecular docking targeting the isethionate binding site of IsIA. Based on striking docking scores, nine compounds showed strong interaction with critical IsIA residues (Arg189, Gln193, Glu470, Cys468, and Arg678), drug-like features, appropriate adsorption, metabolism, excretion, and excretion profile with non-toxicity. Molecular dynamics simulations uncovered the significant impact of binding the compounds on protein conformational dynamics. Finally, binding free energies revealed substantial binding affinity (ranging from -35.23 to -53.88 kcal/mol) of compounds (ZINC913876497, ZINC913856647, ZINC914263733, ZINC914137795, ZINC915757996, ZINC914357083, ZINC913934833, ZINC9143362047, and ZINC913854740) for IsIA. The compounds proposed herein through a multi-faceted computational strategy can be experimentally validated as potential substrate antagonists of B. wadsworthia's IsIA for developing new medications to curb gut-associated illness in the future., 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.)

There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. The currently available antidiabetic therapies are long-term complicated and side effect-prone, and this has led to a demand for more affordable and more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. In this research work, we have focused our efforts to synthesize a series of 1,2,4-triazole-based bis-hydrazones and evaluated their antidiabetic properties. In addition, the precise structures of the synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1 H-NMR, 13 C-NMR, and HREI-MS. To find the antidiabetic potentials of the synthesized compounds, in vitro α-glucosidase and α-amylase inhibitory activities were characterized using acarbose as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both α-amylase and α-glucosidase enzymes was due to the different substitution patterns of the substituent(s) at variable positions of both aryl rings A and B. The results of the antidiabetic assay were very encouraging and showed moderate to good inhibitory potentials with IC 50 values ranging from 0.70 ± 0.05 to 35.70 ± 0.80 μM (α-amylase) and 1.10 ± 0.05 to 30.40 ± 0.70 μM (α-glucosidase). The obtained results were compared to those of the standard acarbose drug (IC 50 = 10.30 ± 0.20 μM for α-amylase and IC 50 = 9.80 ± 0.20 μM for α-glucosidase). Specifically, compounds 17 , 15 , and 16 were found to be significantly active with IC 50 values of 0.70 ± 0.05, 1.80 ± 0.10, and 2.10 ± 0.10 μM against α-amylase and 1.10 ± 0.05, 1.50 ± 0.05, and 1.70 ± 0.10 μM against α-glucosidase, respectively. These findings reveal that triazole-containing bis-hydrazones act as α-amylase and α-glucosidase inhibitors, which help develop novel therapeutics for treating type-II diabetes mellitus and can act as lead molecules in drug discovery as potential antidiabetic agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Benzofuran and 1,3,4-oxadiazole are privileged and versatile heterocyclic pharmacophores which display a broad spectrum of biological and pharmacological therapeutic potential against a wide variety of diseases. This article reports in silico CADD (computer-aided drug design) and molecular hybridization approaches for the evaluation of the chemotherapeutic efficacy of 16 S-linked N -phenyl acetamide moiety containing benzofuran-1,3,4-oxadiazole scaffolds BF1-BF16 . This virtual screening was carried out to discover and assess the chemotherapeutic efficacy of BF1-BF16 structural motifs as Mycobacterium tuberculosis polyketide synthase 13 (Mtb Pks13) enzyme inhibitors. The CADD study results revealed that the benzofuran clubbed oxadiazole derivatives BF3 , BF4 , and BF8 showed excellent and remarkably significant binding energies against the Mtb Pks13 enzyme comparable with the standard benzofuran-based TAM-16 inhibitor. The best binding affinity scores were displayed by 1,3,4-oxadiazoles-based benzofuran scaffolds BF3 (-14.23 kcal/mol), BF4 (-14.82 kcal/mol), and BF8 (-14.11 kcal/mol), in comparison to the binding affinity score of the standard reference TAM-16 drug (-14.61 kcal/mol). 2,5-Dimethoxy moiety-based bromobenzofuran-oxadiazole derivative BF4 demonstrated the highest binding affinity score amongst the screened compounds, and was higher than the reference Pks13 inhibitor TAM-16 drug. The bindings of these three leads BF3 , BF4 , and BF8 were further confirmed by the MM-PBSA investigations in which they also exhibited strong bindings with the Pks13 of Mtb. Moreover, the stability analysis of these benzofuran-1,3,4-oxadiazoles in the active sites of the Pks13 enzyme was achieved through molecular dynamic (MD) simulations at 250 ns virtual simulation time, which indicated that these three in silico predicted bio-potent benzofuran tethered oxadiazole molecules BF3 , BF4 , and BF8 demonstrated stability with the active site of the Pks13 enzyme.

Intensive and inefficient exploitation of pesticides through modernized agricultural practices has caused severe pesticide contamination problems to the environment and become a crucial problem over a few decades. Due to their highly toxic and persistent properties, they affect and get accumulated in non-target organisms, including microbes, algae, invertebrates, plants as well as humans, and cause severe issues. Considering pesticide problems as a significant issue, researchers have investigated several approaches to rectify the pesticide contamination problems. Several analyses have provided an extensive discussion on pesticide degradation but using specific technology for specific pesticides. However, in the middle of this time, cleaner techniques are essential for reducing pesticide contamination problems safely and environmentally friendly. As per the research findings, no single research finding provides concrete discussion on cleaner tactics for the remediation of contaminated sites. Therefore, in this review paper, we have critically discussed cleaner options for dealing with pesticide contamination problems as well as their advantages and disadvantages have also been reviewed. As evident from the literature, microbial remediation, phytoremediation, composting, and photocatalytic degradation methods are efficient and sustainable and can be used for treatment at a large scale in engineered systems and in situ. However, more study on the bio-integrated system is required which may be more effective than existing technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diabetes is also known as a critical and noisy disease. Hyperglycemia, that is, increased blood glucose level is a common effect of uncontrolled diabetes, and over a period of time can cause serious effects on health such as blood vessel damage and nervous system damage. However, many attempts have been made to find suitable and beneficial solutions to overcome diabetes. Considering this fact, we synthesized a novel series of indoline-2,3-dione-based benzene sulfonamide derivatives and evaluated them against α-glucosidase and α-amylase enzymes. Out of the synthesized sixteen compounds ( 1-16 ), only three compounds showed better results; the IC 50 value was in the range of 12.70 ± 0.20 to 0.90 ± 0.10 μM for α-glucosidase against acarbose 11.50 ± 0.30 μM and 14.90 ± 0.20 to 1.10 ± 0.10 μM for α-amylase against acarbose 12.20 ± 0.30 μM. Among the series, only three compounds showed better inhibitory potential such as analogues 11 (0.90 ± 0.10 μM for α-glucosidase and 1.10 ± 0.10 μM for α-amylase), 1 (1.10 ± 0.10 μM for α-glucosidase and 1.30 ± 0.10 μM for α-amylase), and 6 (1.20 ± 0.10 μM for α-glucosidase and 1.60 ± 0.10 μM for α-amylase). Molecular modeling was performed to determine the binding affinity of active interacting residues against these enzymes, and it was found that benzenesulfonohydrazide derivatives can be indexed as suitable inhibitors for diabetes mellitus., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The present study analyzes the determinants and patterns of the regional, local, and differential plant diversity of two different sites with similar climatic but varied edaphic factors. This research was undertaken to study the plant diversity and population structure as a consequence of variation in the soil quality between two biotopes: Guru Ghasidas Vishwavidyalaya in Koni (site-I) and National Thermal Power Corporation in Sipat (site-II). The soil of site-I was found to be fertile and showed rich vegetation. On the other hand, the soil of site II was found to be contaminated with heavy metals, which impacts the flora of the region. The ecology of both sites was studied, and their quantitative and qualitative aspects were compared and contrasted. The abundance, density, and richness of the plants in site II were fairly lower than in site-I, which was confirmed by utilizing Simpson's and Shannon's diversity indices. Many of the species collected from site II were heavy metal accumulators and could also serve as indicators of heavy metal toxicity.

Antioxidant small molecules can prevent or delay the oxidative damage caused by free radicals. Herein, a structure-based hybridization of two natural antioxidants (caffeic acid and melatonin) afforded a novel hybrid series of indole-based amide analogues which was synthesized with potential antioxidant properties. A multiple-step scheme of in vitro radical scavenging assays was carried out to evaluate the antioxidant activity of the synthesized compounds. The results of the DPPH assay demonstrated that the indole-based caffeic acid amides are more active free radical scavenging agents than their benzamide analogues. Compared to Trolox, a water-soluble analogue of vitamin E, compounds 3a , 3f , 3h , 3j , and 3m were found to have excellent DPPH radical scavenging activities with IC 50 values of 95.81 ± 1.01, 136.8 ± 1.04, 86.77 ± 1.03, 50.98 ± 1.05, and 67.64 ± 1.02 µM. Three compounds out of five ( 3f , 3j , and 3m ) showed a higher capacity to neutralize the radical cation ABTS •+ more than Trolox with IC 50 values of 14.48 ± 0.68, 19.49 ± 0.54, and 14.92 ± 0.30 µM, respectively. Compound 3j presented the highest antioxidant activity with a FRAP value of 4774.37 ± 137.20 μM Trolox eq/mM sample. In a similar way to the FRAP assay, the best antioxidant activity against the peroxyl radicals was demonstrated by compound 3j (10,714.21 ± 817.76 μM Trolox eq/mM sample). Taken together, compound 3j was validated as a lead hybrid molecule that could be optimized to maximize its antioxidant potency for the treatment of oxidative stress-related diseases.

Polymer grafting is a technique to improve the morphology, chemical, and physical properties of the polymer. This technique has the potential to improve the existing conduction and properties of polymers other than charge transport; as a result, it enhances the solubility, nano-dimensional morphology, biocompatibility, bio-communication, and other property of parent polymer. A polymer's physicochemical properties can be modified even further by creating a copolymer with another polymer or by grafting. Here in the various chemical approaches for polymer grafting, like free radical, click reaction, amide formation, and alkylation have been discussed with their importance, moreover the process and its importance are covered comprehensively with their scientific explanation. The present review also covers the effectiveness of the graft-to approaches and its application in various fields, which will give reader a glimpse about polymer grafting and its uses., 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 © 2023 Purohit, Bhatt, Mittal, Abdellattif and Farghaly.)

The Coronavirus pandemic, Covid-19 and SARS-Cov-2 put multidisciplinary research by chemists, biologists, pharmacists and theorists necessary and primordial task to find new active biomolecules which will be beneficial for all humanity. The azoles drugs are electronic rich, they should be used with caution, and an understanding of their pharmacokinetic profile, safety, absorption, distribution, excretion, metabolism, toxicity, and drug-drug interaction profiles is important to provide effective and cure therapy. In these objectives and goals, twenty aromatic nitrogen heterocycle compounds were chosen for in silico, docking and AMET studies against SARS-CoV-2. In this paper with respect to the protein S of SARS-CoV-2 properties, the GAUSSIAN 09w program used in the semi-empirical method at the AM1 level with the optimization of the geometry of the structures. Then Toxicity and physicochemical properties were evaluated by AMET. Molecular docking investigations conducted; the binding affinities as well as interactions of the sieve compounds with the SRAS-CoV-2 protein Spike using PyRx software. In general, the preliminary results are fructuous and needs further in vitro testes., 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., (Copyright © 2023 Elsevier Ltd. All rights reserved. Selection and peer-review under responsibility of the scientific committee of the Fifth edition of the International Conference on Materials & Environmental Science.)

Macrocycle-based amphiphiles are capable of self-assembling into multidimensional nano-architecture with defined dimensions for various applications. Herein we report the synthesis, physio-chemical characterizations and oral drug delivery profiling of resorcinarene-based amphiphilic supramolecular macrocycle. The macrocycle was synthesized in two-step reaction and characterized using 1 H NMR, Mass spectrometry and IR spectroscopic techniques. The synthesized macrocycle was assessed for vesicles formation, checked for biocompatibility and then Amphotericin B (Amp-B) was entrapped in macrocycle-based vesicles. The drug loaded vesicles were characterized for shape, size, homogeneity, drug entrapment, surface charge, in-vitro release profile and stability. Amp-B loaded macrocycle based vesicles were examined in rabbits for in-vivo bioavailability and compared with plan drug suspension. The synthesized macrocycle was non-toxic in normal mouse fibroblast cells, compatible with blood and safe in mice. The drug loaded macrocycle based vesicles appeared spherical with 279.4 nm size and - 12.2 mV zeta potential loading 85.45 % drug. The drug loaded vesicles storage stability for 30 days and gastric fluid stability for 1 h were it retained nearly 90 % drug at 30th day and 83.79 % drug at 1 h in gastric fluid. Oral bioavailability of Amp-B in rabbits was markedly enhanced when delivered in synthesized macrocycle based vesicles in comparison with plan drug suspension. Results of this study indicate that the synthesized star shaped tetra-tailed supramolecular amphiphile could be used as an efficient nanocarrier for enhancing oral bioavailability of drugs with solubility and bioavailability issues like Amp-B., Competing Interests: Conflicts of interest All authors declare, they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study was carried out to synthesize benzotriazole-based bis-Schiff base scaffolds ( 1 - 20 ) and assess them in vitro for α -glucosidase inhibitory potentials. All the synthetics analogs based on benzotriazole-based bis-Schiff base scaffolds were found to display an outstanding inhibition profile on screening against the α -glucosidase enzyme. The synthetic scaffolds showed a varied range of inhibition profiles having IC 50 values ranging from 1.10 ± 0.05 µM to 28.30 ± 0.60 µM when compared to acarbose as a standard drug (IC 50 = 10.30 ± 0.20 µM) . Among the series, fifteen scaffolds 1 - 3 , 5 , 6 , 9 - 16 , 18 - 20 were identified to be more potent than standard acarbose, while the five remaining scaffolds 4 , 7 , 8 , 16, and 17 , also showed potency against the α -glucosidase enzyme but were found to be less potent than standard acarbose. The structure of all the newly synthesized scaffolds was confirmed using different spectroscopic techniques such as HREI-MS and 1 H- and 13 C- NMR spectroscopy. To find a structure-activity relationship, molecular docking studies were carried out to understand the binding mode of the active inhibitors with the active sites of the enzyme and the results supported the experimental data.

Hepatitis causes liver infection leading to inflammation that is swelling of the liver. They are of various types and detrimental to human beings. Natural products have recently been used to develop antiviral drugs against severe viral infections like viral hepatitis. They are usually extracted from herbs or plants and animals. The naturally derived compounds have demonstrated significant antiviral effects against the hepatitis virus and they interfere with different stages of the life cycle of the virus, viral release, replication, and its host-specific interactions. Antiviral activities have been demonstrated by natural products such as phenylpropanoids, flavonoids, xanthones, anthraquinones, terpenoids, alkaloids, aromatics, etc., against hepatitis B and hepatitis C viruses. The recent studies conducted to understand the viral hepatitis life cycle, more effective naturally derived drugs are being produced with a promising future for the treatment of the infection. This review emphasizes the current strategies for treating hepatitis, their shortcomings, the properties of natural products and their numerous types, clinical trials, and future prospects as potential drugs., 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 © 2022 Roy, Roy, Gacem, Datta, Zeyaullah, Muzammil, Farghaly, Abdellattif, Yadav and Simal-Gandara.)

Human carbonic anhydrase inhibitors (hCAIs) are a key therapeutic class with a multitude of novel applications such as anticonvulsants, topically acting antiglaucoma, and anticancer drugs. Herein, a new series of 4-anilinoquinazoline-based benzenesulfonamides were designed, synthesised, and biologically assessed as potential hCAIs. The target compounds are based on the well-tolerated kinase scaffold (4-anilinoquinazoline). Compounds 3a (89.4 nM), 4e (91.2 nM), and 4f (60.9 nM) exhibited 2.8, 2.7, and 4 folds higher potency against hCA I when compared to the standard (AAZ, V ), respectively. A single digit nanomolar activity was elicited by compounds 3a (8.7 nM), 4a (2.4 nM), and 4e (4.6 nM) with 1.4, 5, and 2.6 folds of potency compared to AAZ (12.1 nM) against isoform hCA II, respectively. Structure-activity relationship (SAR) and molecular docking studies validated our design approach that revealed highly potent hCAIs.

Nanoparticles are inevitable byproducts of modern industry. However, the environmental impacts arising from industrial applications of nanoparticles are largely under-reported. This study evaluated the ecotoxicological effects of aluminum oxide nanoparticles (Al 2 O 3 NP) and its influence on sulfacetamide (SA) biodegradation by a freshwater microalga, Scenedesmus obliquus. Although Al 2 O 3 NP showed limited toxicity effect on S. obliquus, we observed the toxicity attenuation aspect of Al 2 O 3 NP in a mixture of sulfacetamide on microalgae. The addition of 100 mg L -1 of Al 2 O 3 NP and 1 mg L -1 of SA reduced total chlorophyll by 23.3% and carotenoids by 21.6% in microalgal compared to control. The gene expression study demonstrated that ATPF0C, Lhcb1, HydA, and psbA genes responsible for ATP synthesis and the photosynthetic system were significantly downregulated, while the Tas gene, which plays a major role in biodegradation of organic xenobiotic chemicals, was significantly upregulated at 1 and 100 mg L -1 of Al 2 O 3 NP. The S. obliquus removed 16.8% of SA at 15 mg L -1 in 14 days. However, the removal was slightly enhanced (18.8%) at same concentration of SA in the presence of 50 mg L -1 Al 2 O 3 NP. This result proves the stability of sulfacetamide biodegradation capacity of S. obliquus in the presence of Al 2 O 3 NP co-contamination. The metabolic analysis showed that SA was degraded into simpler byproducts such as sulfacarbamide, sulfaguanidine, sulfanilamide, 4-(methyl sulfonyl)aniline, and N-hydroxy-benzenamine which have lower ecotoxicity than SA, demonstrating that the ecotoxicity of sulfacetamide has significantly decreased after the microalgal degradation, suggesting the environmental feasibility of microalgae-mediated wastewater technology. This study provides a deeper understanding of the impact of nanoparticles such as Al 2 O 3 NP on aquatic ecosystems., 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 © 2022 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) is one of the globally worst killer diseases. In this study, the in vitro and in vivo antidiabetic activity and antioxidant capacity were determined and the phytochemical analyses were carried out on flower extract and sub-extracts of Rhaponticoides iconiensis . The in vitro antidiabetic activity was tested with α-amylase and α-glucosidase enzyme inhibition methods and an in vivo OGTT test in healthy and alloxan-induced rats. Although, the antioxidant activity was investigated with DPPH ● , ABTS ●+ and FRAP tests, the phytochemical composition analysis was carried out by LC-MS/MS. The highest α-glucosidase and α-amylase activity even from positive control acarbose were found in the ethyl acetate sub-extract of R. iconiensis (IC 50 = 11.737 ± 0.823 µg/mL and 84.247 ± 0.721 µg/mL, respectively). This sub-extract also was active according to the results of in vivo tests. Moreover, the highest antioxidant activity on DPPH ● (IC 50 = 0.126 ± 0.002 mg/mL), FRAP (at a concentration of 1 mg/mL equivalent to 3112.052 ± 2.023 mmol Fe 2+ ) and ABTS +● (at a concentration of 0.5 mg/mL equivalent to 0.608 ± 0.005 µM Trolox) tests. In addition, LC-MS/MS analyses of the active sub-extract revealed mainly the presence of patuletin, patuletin 3,7-diglucoside, naringin and 3,4-dicaffeoylquinic acid detected in the active sub-extract. In silico molecular docking and dynamics simulations studies were performed on these compounds with α-amylase and α-glucosidase enzymes for protein-ligand interactions and stability.

Saccharine is a pharmacologically significant active scaffold for various biological activities, including antibacterial and anticancer activities. Herein, saccharinyl hydrazide ( 1 ) was synthesized and converted into 2-[(2Z)-2-(1,1-dioxo-1,2-dihydro-3H-1λ 6 ,2- benzothiazole-3-ylidene) hydrazinyl] acetohydrazide ( 5 ), which was employed as a key precursor for synthesizing a novel series of small molecules bearing different moieties of monosaccharides, aldehydes, and anhydrides. Potent biological activities were found against Staphylococcus and Escherichia coli , and the results indicated that compounds 6c and 10a were the most active analogs with an inhibition zone diameter of 30-35 mm . In cell-based anticancer assay over Ovcar-3 and M-14 cell lines, compound 10a was the most potent analog with IC 50 values of 7.64 ± 0.01 and 8.66 ± 0.01 µM, respectively. The Petra Orisis Molinspiration (POM) theoretical method was used to calculate the drug score of tested compounds and compare them with their experimental screening data. Theoretical DFT calculations were carried out in a gas phase in a set of B3LYP 6-311G (d,p). Molecular docking studies utilizing the MOE indicated the best binding mode with the highest energy interaction within the binding sites. The molecular docking for Ovcar-3 was carried out on the ovarian cancer protein (3W2S), while the molecular docking for M-14 melanoma was carried out on the melanoma cancer protein (2OPZ). The MD performed about 2ns simulations to validate selected compounds' theoretical 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 © 2022 Abdellattif, Elkamhawy, Hagar, Hadda, Shehab, Mansy, Belal, Arief and Hussien.)

Nowadays, nanotechnology is gaining interest on diagnostics for several chronic diseases. In the present study, the chemical oxidative method of aniline in acid medium with ammonium peroxydisulfate (APS) as an oxidant was employed to develop polyaniline (PANI)-based nanocomposite overflowing/doping on ZnO. The chemical properties, morphology, and structure of the polymer and nanocomposite were investigated using FTIR, XRD, and SEM. The characteristic FTIR peaks of PANI were reported to shift to a higher or lower wave number in PANI-doped ZnO composites due to the formation of H-bonding. Different amounts of ZnO nanoparticles were used to test this influence on the strength of the generated materials. The ability of the PANI-doped ZnO nanocomposite to inhibit struvite crystal growth was determined. The size of struvite crystals was condensed from 2.9 to 1.4 cm at a concentration of 5% PANI-doped ZnO nanoparticles, and the inhibition efficiency of synthesized PANI-doped ZnO against kidney stone (struvite) was confirmed by molecular docking analyzes. The in vitro as well as in silico study revealed the potential applications of polyaniline/ZnO nanocomposite in kidney diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel series of bis -[1,3,4]thiadiazolimines, and bis -thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1'-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α -haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the M pro of SARS-CoV-2. The best compound, 5h , has average binding energy (-7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (-7.36 ± 0.34 and -6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the M pro using the PLIP web server were analyzed.

Inhibition of PDE5 results in elevation of cGMP leading to vascular relaxation and reduction in the systemic blood pressure. Therefore, PDE5 inhibitors are used as antihypertensive and antianginal agents in addition to their major use as male erectile dysfunction treatments. Previously, we developed a novel series of 34 pyridopyrazinone derivatives as anticancer agents (series A - H ). Herein, a multi-step in silico approach was preliminary conducted to evaluate the predicted PDE5 inhibitory activity, followed by an in vitro biological evaluation over the enzymatic level and a detailed SAR study. The designed 2D-QSAR model which was carried out to predict the IC 50 of the tested compounds revealed series B , D , E and G with nanomolar range of IC 50 values (6.00-81.56 nM). A further docking simulation model was performed to investigate the binding modes within the active site of PDE5. Interestingly, most of the tested compounds showed almost the same binding modes of that of reported PDE5 inhibitors. To validate the in silico results, an in vitro enzymatic assay over PDE5 enzyme was performed for a number of the promising candidates with different substitutions. Both series E and G exhibited a potent inhibitory activity (IC 50 = 18.13-41.41 nM). Compound 11b (series G , oxadiazole-based derivatives with terminal 4-NO 2 substituted phenyl ring and rigid linker) was the most potent analogue with IC 50 value of 18.13 nM. Structure-activity relationship (SAR) data attained for various substitutions were rationalized. Furthermore, a molecular dynamic simulation gave insights into the inhibitory activity of the most active compound ( 11b ). Accordingly, this report presents a successful scaffold repurposing approach that reveals compound 11b as a highly potent nanomolar PDE5 inhibitor worthy of further investigation.

Using stationary electrochemical, polarization resistance, cathodic charging, transient electrochemical impedance spectroscopy, and theoretical and molecular mechanics studies, epoxy polymer-coated carbon steel specimens' ability to protect metals from corrosion in various soil extracts was examined. According to the polarization resistance tests results, the polymer coating remained stable for 60 days in all three soil extracts, with a 90% efficiency for the steel coated in Soil Extract A, indicating that the sandy soil is less aggressive than the other two. The aggressiveness of clay soil was confirmed by the fact that a polymer-coated steel rod in the clay soil extract experienced a corrosion current density of 97 µA/cm 2 . In contrast, the same rod in sandy soil had a current density of 58 µA/cm 2 . The coating's good adsorption contact with the metal surface was further guaranteed by molecular dynamics simulations, which provided atomic-level evidence of the epoxy molecule's adsorption behavior (geometry) and adsorption energy on the carbon steel surface.

Investigating novel compounds that may be useful in designing new, less toxic, selective, and potent breast anticancer agents is still the main challenge for medicinal chemists. Thus, in the present work, acetylthiophene was used as a building block to synthesize a novel series of thiazole-bearing thiophene derivatives. The structures of the synthesized compounds were elucidated based on elemental analysis and spectral measurements. The cytotoxic activities of the synthesized compounds were evaluated against MCF-7 tumor cells and compared to a cisplatin reference drug, and against the LLC-Mk2 normal cell line using the MTT assay, and the results revealed promising activities for compounds 4b and 13a . The active compounds were subjected to molecular modeling using MOE 2019, the pharmacokinetics were studied using SwissADME, and a toxicity radar was obtained from the biological screening data. The results obtained from the computational studies supported the results obtained from the anticancer biological studies.

Despite the fact that there are already drugs for cancer, they still show strong toxicity to the human organism. That is why it is necessary to establish the factors affecting activity in order to develop new, more effective drugs aimed at tumor cells, minimizing harm to healthy cells. The present research is based on electronic properties calculation of the complexes using AlteQ approach. In the focus of this study are complexes of human dihydrofolate reductase (hDHFR) with a series of known inhibitors bound in the active site. Further, a statistical analysis was performed to establish the relationships between a myriad electronic characteristics and IC 50 . The change in total volume and the change of own electrons number of hydrogen atoms in their atomic basins are identified as the descriptors correlating the most with the hDHFR inhibition potency. Additionally, two lipophilic parts of protein (Thr56, Ser59, Ile60 and Ile7, Val8, Ala9) were found, which act as a key factor in decreasing bioactivity. The depth analysis of intermolecular interactions showed that the interactions between water molecules and ligand play a crucial role in hDHFR inhibition. Furthermore, the molecular dynamics simulations were used for deeper understanding of the structural inhibition, each for 50 ns time scale in explicit water conditions. Thus, the AlteQ approach made it possible to determine the factors influencing the activity and evaluate them not only qualitatively, but also quantitatively.Communicated by Ramaswamy H. Sarma.

Drug resistance in Mycobacterium tuberculosis has become a major challenge to the current regime of treatment as well as to the containment of the disease globally. The molecular and genetic studies identified frequently occurring point mutations in the virulent protein such as KatG of M. tuberculosis resulted in the development of isoniazid tolerance in the pathogen. This study aims to analyze the structural basis of the disease mutations available in the literature as well as to predict novel alteration in the KatG which may cause similar deleterious effects. Around 15 experimentally derived mutations were included in this study and pathogenic mutational landscapes containing 60 site-specific alterations were predicted using the available in silico techniques. The effects of these mutations on the stability of the protein were studied and an exhaustive docking study was conducted for each classified perturbations, which identify the highest changes in the binding energies in p.Meth255Ile among experimental and p.Ala222Arg in computationally predicted mutations. Furthermore, the structural effects on these substitutions were analyzed using the principles of molecular dynamic simulations each for a 100 ns time scale, which validated the interaction studies. The outcome of this study may enable the identification of the novel drug resistance-associated point mutations which were not previously reported and may contribute significantly in a variety of experimental studies as well as facilitate the process of drug design and discovery.Communicated by Ramaswamy H. Sarma.

A new family of pyrazole-based compounds ( 1 - 15 ) was synthesized and characterized using different physicochemical analyses, such as FTIR, UV-Visible, 1 H, 13 C NMR, and ESI/LC-MS. The compounds were evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. The results indicate that some compounds showed excellent antibacterial activity against E. coli , S. aureus , C. freundii , and L. monocytogenes strains. In contrast, none of the compounds had antifungal activity. Molecular electrostatic potential (MEP) map analyses and inductive and mesomeric effect studies were performed to study the relationship between the chemical structure of our compounds and the biological activity. In addition, molecular docking and virtual screening studies were carried out to rationalize the antibacterial findings to characterize the modes of binding of the most active compounds to the active pockets of NDM1 proteins.

Despite the challenging conditions in the pre-Saharan areas of Algeria, such as weak plant cover and a harsh climate, beekeeping is being developed and spread. In the present work, honey samples collected from ten locations in the El Oued region were examined during the spring of 2021. A melissopalynological analysis was carried out, followed by a floristic investigation. The 10 honey samples were also investigated for their physicochemical properties and antioxidant and antibacterial activity against five strains: Escherichia coli , Staphylococcus aureus , Bacillus subtilus , Listeria innocua, and Micrococcus luteus. The floristic analysis found 65 species belonging to 33 botanical families, with a dominance of the Asteraceae family accounting for 18.461% of the total. The melissopalynological study revealed only one monofloral honey ( Ziziphus lotus ), whereas the nine others were multi-floral. The honey's color changed from light to dark amber, and most tested honey was of high quality, fulfilling international criteria. The total phenol and flavonoid contents varied considerably amongst the various honey samples. Furthermore, LC-MS-MS phenolic profile analysis identified the presence of 20 chemicals, of which only three phenols were found in all honey types. Antioxidant capacity analyzed with FRAP test and antiradical activities against DPPH differed from one honey sample to another. Moreover, a significant correlation was recorded between the antioxidant activity, honey's color, polyphenol, and flavonoid contents. The S. aureus strain was the most sensitive regarding honey antibacterial activity, while M. luteus and B. subtilis strains were only moderately sensitive.

New quinazoline derivatives were designed based on the structural modification of the reported inhibitors to enhance their selectivity toward Aurora A. The synthesized compounds were tested over Aurora A, and a cytotoxicity assay was performed over NCI cell lines to select the best candidate for further evaluation. Compound 6e (2-(3-bromophenyl)-8-fluoroquinazoline-4-carboxylic acid) was the most potent compound among the tested derivatives. A Kinase panel assay was conducted for compound 6e over 14 kinases to evaluate its selectivity profile. Further cell cycle and apoptosis analysis were evaluated for compound 6e over the MCF-7 cell line at its IC 50 of 168.78 µM. It arrested the cell cycle at the G1 phase and induced apoptosis. Molecular docking was performed to explore the possible binding mode of compound 6e into the active site. It showed significant binding into the main pocket in addition to potential binding interactions with the key amino acid residues. Accordingly, compound 6e can be considered a potential lead for further structural and molecular optimization of the quinazoline-based carboxylic acid scaffold for Aurora A kinase selective inhibition with apoptosis properties.

Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both the MMP-2 and MMP-9 proteins to find the most promising inhibitors as a proposed computational mechanism to treat keratoconus. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, and MMP inhibitors (MMPIs) are usually designed to interact with zinc ion in the catalytic (CAT) domain, thus interfering with enzymatic activity. In our research work, the FDA-approved ophthalmic medications will be investigated as MMPIs, to explore if they can be repurposed for KC treatment. The obtained findings of the docking study suggest that atenolol and ampicillin are able to accommodate into the active sites of MMP-2 and MMP-9. Additionally, both exhibited binding modes similar to inhibitors used as references, with an ability to bind to the zinc of the CAT. Molecular dynamic simulations and the MM-GBSA binding free-energy calculations revealed their stable binding over the course of 50 ns. An additional pharmacophoric study was carried out on MMP-9 (PDB ID: 1GKC) using the co-crystallized ligand as a reference for the future design and screening of the MMP-9 inhibitors. These promising results open the door to further biological research to confirm such theoretical results.

Concerns have been raised about the high number of mutations in the spike protein of the new emergence of the highly transmissible Omicron variant (B.1.1529 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This variant's extraordinary ability to evade antibodies would significantly impair the current vaccination program. This present study aimed to computationally analyze the interaction between the receptor-binding domain (RBD) in the spike protein of Omicron variants and human angiotensin-converting enzyme 2 (hACE2). The docking results indicated that Omicron BA.2 has exceptionally strong interactions with hACE2 in comparison to Omicron BA.1, Delta, and wild-type, as indicated by various parameters such as salt bridge, hydrogen bond, and non-bonded interactions. The results of the molecular dynamics simulation study corroborate these findings, indicating that Omicron BA.2 has a strong and stable interaction with hACE2. This study provides insight into the development of an effective intervention against this variant.