Compounds 4g Research Articles

Semi-Preparation and X-ray Single-Crystal Structures of Sophocarpine-Based Isoxazoline Derivatives and Their Pesticidal Effects and Toxicology Study.

Recently, research and development of novel pesticides from natural plant products have received much attention. To accelerate the application of sophocarpine as the agrochemical candidate, a series of novel sophocarpine-based isoxazoline derivatives were prepared by the 1,3-dipolar [2 + 3] cycloaddition reaction of sophocarpine with different chloroximes. Their structures were well characterized by high-resolution mass spectra, infrared spectra, and proton/carbon-13 nuclear magnetic resonance spectra. Eight steric configurations of compounds 5a, 5e', 5f, 5g, 5h, 5i, 5r, and 5u' were further determined by X-ray single-crystallography. Against Aphis citricola Van der Goot, compounds 5n (LD50: 0.032 μg/nymph) and 5o (LD50: 0.024 μg/nymph) exhibited greater than 3.7- and 4.9-fold potent aphicidal activity compared to sophocarpine (LD50: 0.118 μg/nymph). Against Tetranychus cinnabarinus Boisduval, derivative 5g displayed the most promising acaricidal activity with the LC50 value of 0.247 mg/mL, which was 14.2-fold that of sophocarpine. Compounds 5d and 5g also exhibited good control efficacy against T. cinnabarinus. Scanning electron microscopy images indicated that compound 5g can destroy the mite cuticle layer. These results will provide the foundation for the structural modification and use of sophocarpine derivatives as agrochemicals in the future.

Synthesis of new 1,4-dihydropyridine derivative, anti-cancer, bacterial activity, molecular docking and adsorption, distribution, metabolism and excretion analysis.

Aim: The amination and cyclization method developed a new strategy for designing and assembling new 1,4-dihydropyridine derivatives of compounds 3a-g and 4a-g.Methods & materials: Newly prepared pyridine compounds are more economical, and reduce the reaction time. FT-IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses elucidated the synthesized derivatives. All the derivatives are subjected to in vitro assay against MCF-7 (breast) and anti-bacterial activity.Results: In the anti-bacterial activity compound 3c is moderately active against Escherichia coli (6.0g/ml), and 4c is extremely active against Lactiplantibacillus plantarum (10.0g/ml) compared with standard Erythromycin. In cytotoxic activity, the compound 3g (lC50 24.5μM) is slightly active against standard doxorubicin. We also present the outcome of a molecular docking study connecting the methoxsalen (Protein Data Bank, PDB ID: 1Z11). Compound 3g shows a higher binding affinity (-7.7Kcal/mol) matching up with doxorubicin(-9.0Kcal/mol). The synthesized analogs were predicted for their adsorption, distribution, metabolism and excretion profiles and pharmacokinetics. The compound 3g has three rotatable bonds (NROB≤10), five hydrogen bond acceptors (HBA≤10) and four hydrogen bond donors (HBD≤5). All the compounds follow Lipinski's rule.Conclusion: Therefore, the compounds 3c and 3g are used as cytotoxic and anti-bacterial drugs in feature.

Synthesis and Molecular Docking of Curcumin-Derived Pyrazole-Thiazole Hybrids as Potent α-Glucosidase Inhibitors.

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 IC50 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 (IC50 = 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.

Discovery and Development of Caffeic Acid Analogs as Versatile Therapeutic Agents

Caffeic acid (CA) is a polyphenolic acid compound widely distributed in plant seeds. As natural compounds with high research interest, caffeic acid and its derivatives show good activity in the treatment of tumors and inflammation and have antibacterial properties. In recent years, caffeic acid derivatives have been studied extensively, and these derivatives fall roughly into three categories: (1) caffeic acid ester derivatives, (2) caffeic acid amide derivatives, (3) caffeic acid hybrids. These caffeic acid analogues exert mainly antibacterial and antioxidant activities. Among the caffeic acid analogues summarized in this paper, compounds 1g and CAP10 have good activity against Candida albicans, and their MIC50 is 32 µg/mL and 13 μM, respectively. In a DPPH assay, compounds 3k, 5a, CS2, Phellinsin A and 8j showed strong antioxidant activity, and their IC50 values are 18.6 μM, 67.85 μM, 40.29 μM, 0.29 ± 0.004 mM, 4774.37 ± 137.20 μM, respectively. Overall, compound CAP10 had the best antibacterial activity and compound 3k had the best antioxidant activity. This paper mainly summarizes and discusses some representative caffeic acid analogs, hoping to provide better drug design strategies for the subsequent development of caffeic acid analogs.

Synthesis of Tetrahydrocarbazole-Tethered Triazoles as Compounds Targeting Telomerase in Human Breast Cancer Cells

Telomere shortening and the induction of senescence and/or cell death may result from inhibition of telomerase activity in cancer cells. Herein, the properties of carbazole–triazole compounds targeting telomerase in human breast cancer cells are explored. All derivatives were evaluated for loss of viability in MCF-7 breast cancer cells, with compound 5g identified as the most potent within the examined series. Green synthesis was employed using water, a reusable nano-Fe2O3-catalyzed reaction, and an electrochemical method for the synthesis of tetrahydrocarbazole and triazoles. The crystal data of compound 4 is also reported. Furthermore, in silico analysis predicted that compound 5g may target human telomerase. Molecular docking analysis of compound 5g towards hTERT predicted a binding affinity of −6.74 kcal/mol. In flow cytometry assays, compound 5g promoted apoptosis and cell cycle arrest in the G2-M phase. Finally, compound 5g inhibited the enzymatic activity of telomerase in human breast cancer cells. In conclusion, a green synthesized series of carbazole–triazoles that target telomerase in cancer cells is reported.

Design, Synthesis, and Biological Evaluation of Novel Heterocyclic Derivatives of 2,4‐Thiazolidine Dione as Anti‐Cancer Agents

ABSTRACTThis study explores the development of novel 2,4‐thiazolidinedione derivatives as potential anticancer agents. We report the synthesis of 15 novel analogs utilizing a strategic approach focused on intermediate diversification. Key intermediates, (Z)‐5‐([1,1′‐biphenyl]‐4‐ylmethylene)thiazolidine‐2,4‐dione 5a and (Z)‐5‐(benzo[1,3]dioxol‐5‐ylmethylene)thiazolidine‐2,4‐dione 5b, were synthesized via Knoevenagel condensation and acetal formation reactions, respectively. Subsequent N‐alkylation reactions provided a platform for introducing diverse functionalities and exploring structure–activity relationships to optimize the medicinal chemistry profile of these novel compounds. The synthesized compounds were tested against various human cancer cell lines, including for breast (MCF‐7, MDA‐MB‐453), lung (A549), and prostate (PC‐3) cancers, using an MTT assay. Compounds 8c and 10g emerged as particularly promising, exhibiting activity against all tested cell lines with IC50 values between 3.41 ± 0.51 and 40 μM. These compounds also induced apoptosis, suggesting that they inhibit cell proliferation through this cell death pathway. Moreover, relative molecular docking studies provided evidence that compound 8c likely functions by intercalating with DNA.

The impact of three thioxothiazolidin compounds on trehalase activity and development of Spodoptera frugiperda larvae.

Trehalases (TREs), serving as crucial enzymes regulating trehalose and chitin metabolism in insects, represent prime targets for pest control strategies. We investigated the impact of three thioxothiazolidin compounds (1G, 2G, and 11G) on TRE activity and summarized their effects on the growth and development of Spodoptera frugiperda (Lepidoptera, Noctuidae). The experimental larvae of S. frugiperda were injected with the three thioxothiazolidin compounds (1G, 2G, and 11G), while the control group received an equivalent volume of 2% DMSO as a control. All three compounds had a strong effect on inhibiting TRE activity, significantly prolonging the pre-pupal development stage. However, compared with the 11G-treated group, the survival rate of larvae treated with 1G and 2G was significantly reduced by 31.11% and 27.78% respectively, while the occurrence of phenotypic abnormalities related to growth and development was higher. These results manifest that only the TRE inhibitors, 1G and 2G, modulate trehalose and chitin metabolism pathways of larvae, ultimately resulting in the failure molting and reduction of survival rates. Consequently, the thioxothiazolidin compounds, 1G and 2G, hold potential as environmentally friendly insecticides.

Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular docking insights

Imidazole moieties exhibit a broad range of biological activities, including analgesic, anti-depressant, anticancer, anti-fungal, anti-tubercular, anti-inflammatory, antimicrobial, antiviral, and antifungal properties. In this study, we explored the use of Schiff base for the synthesis of new imidazole derivatives as anti-inflammatory and pain-relieving agents. A series of eight novel imidazole analogues (2a–h) were prepared in three steps with excellent yields. All compounds were characterized using IR, NMR, and mass spectral data. Their analgesic and anti-inflammatory activities were evaluated using hot plate and paw oedema methods. Compound 2 g (1-(2,3-dichlorophenyl)-2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole) showed significant analgesic activity (89% at 100 mg/kg b.w.), while compounds 2a (2-(2,6-dichlorophenyl)-1-(4-ethoxyphenyl)-4,5-diphenyl-1H-imidazole) and 2b (2-(2,3-dichlorophenyl)-1-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole) exhibited good anti-inflammatory activity (100% at 100 mg/kg b.w.), comparable to diclofenac salt (100% at 50 mg/kg b.w.). Molecular docking studies were conducted using Schrödinger software version 2021-2, employing the OPLS4 force field for both receptor and ligand preparation. The results were visualized using molecular visualization software such as PyMOL. These studies revealed that compound 2g exhibited the highest binding affinity with the COX-2 receptor (−5.516 kcal/mol). Compound 2g formed three conventional hydrogen bonds with residues GLN-242 (bond length: 2.3 Å) and ARG-343 (bond lengths: 2.2 Å & 2.4 Å). This binding affinity was comparable to that of Diclofenac salt, which showed the highest binding affinity of −5.627 kcal/mol with the COX-2 receptor. Diclofenac salt formed two conventional hydrogen bonds with the residues ARG-344 (bond length: 2.0 Å) and TRP-140 (bond length: 1.7 Å). Later, molecular dynamic simulations confirmed the stable binding affinity of compound 2g with the protein. Furthermore, other compounds also demonstrated potential binding to the receptor-binding pocket region. The anti-inflammatory potential of the synthesized compounds was evaluated using the carrageenan-induced rat hind paw oedema model, while the analgesic potential was assessed using the hot plate method. These evaluations were conducted in comparison with Diclofenac sodium, serving as the standard compound. However, compound 2g stood out for its superior analgesic activity, as confirmed by in-vivo examination. These findings suggest that these novel imidazole derivatives have potential as anti-inflammatory and analgesic agents.

One-Pot multicomponent synthesis of novel pyrazole-linked thiazolyl-pyrazolines: Molecular docking and cytotoxicity assessment on breast and lung cancer cell-lines

Cancer remains a foremost cause of mortality globally, with approximately 20 million new cases and nearly 10 million deaths reported in 2022. Lung and breast cancers are particularly prevalent and deadly, underscoring the critical need for novel therapeutic strategies. This study utilized a one-pot, multicomponent reaction (MCR) approach to synthesize a novel series of pyrazole-linked thiazolyl-pyrazolines. The optimal reaction conditions were determined by systematically varying bases, temperatures, reaction times, and solvents. The best yield was achieved using NaOH as the base at 50 °C with 2 h of stirring in ethanol. The synthesized compounds underwent thorough characterization through IR, mass spectrometry, and NMR spectroscopy. Molecular docking studies indicated strong binding affinities to the ErbB4 kinase, suggesting potential utility as kinase inhibitors. Compounds 5E, 5F, and 5G exhibited significant cytotoxicity against breast cancer cell lines, with IC50 values ranging from 15.79±1.272 to 28.38±1.520 µM. Meanwhile, compounds 5A, 5B, 5D, and 5G demonstrated potent effects against lung cancer cell lines, with IC50 values between 7.945±0.99 and 9.295±1.074 µM. Remarkably, compound 5G showed potent efficacy against both breast and lung cancers, with IC50 values of 28.38±1.520 µM and 9.02±1.07 µM, respectively. This study illuminates the critical role of pyrazole-linked thiazolyl-pyrazoline scaffolds in crafting powerful cancer therapeutics targeting ErbB4 (HER4) kinase. Unique in its dual functionality, ErbB4 can act as either an oncogene or a tumor suppressor in lung and breast cancers, contingent on specific cellular contexts and isoform variations. The dynamic expression of ErbB4 intricately modulates tumor growth and patient outcomes, marking it as a compelling therapeutic target for innovative treatments in both breast and lung cancer.

Anti-Diabetic Activities and Molecular Docking Studies of Aryl-Substituted Pyrazolo[3,4-b]pyridine Derivatives Synthesized via Suzuki Cross-Coupling Reaction.

Pyrazolo[3,4-b]pyridine scaffolds have been heavily exploited in the development of nitrogen-containing heterocycles with numerous therapeutic applications in the field of medicinal and pharmaceutical chemistry. The present work describes the synthesis of eighteen biaryl pyrazolo[3,4-b]pyridine ester (6a-i) and hydrazide (7a-i) derivatives via the Suzuki cross-coupling reaction. These derivatives were subsequently screened for their therapeutic potential to inhibit the diabetic α-amylase enzyme, which is a key facet of the development of anti-diabetic agents. Initially, the ethyl 4-(4-bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate 4 was synthesized through a modified Doebner method under solvent-free conditions, providing an intermediate for further derivatization with a 60% yield. This intermediate 4 was subjected to Suzuki cross-coupling, reacting with electronically diverse aryl boronic acids to obtain the corresponding pyrazolo[3,4-b]pyridine ester derivatives (6a-i). Following this, the biaryl ester derivatives (6a-i) were converted into hydrazide derivatives (7a-i) through a straightforward reaction with hydrazine monohydrate and were characterized using 1H-NMR, 13C-NMR, and LC-MS spectroscopic techniques. These derivatives were screened for their α-amylase inhibitory chemotherapeutic efficacy, and most of the biaryl ester and hydrazide derivatives demonstrated promising amylase inhibition. In the (6a-i) series, the compounds 6b, 6c, 6h, and 6g exhibited excellent inhibition, with almost similar IC50 values of 5.14, 5.15, 5.56, and 5.20 μM, respectively. Similarly, in the series (7a-i), the derivatives 7a, 7b, 7c, 7d, 7f, 7g, and 7h displayed excellent anti-diabetic activities of 5.21, 5.18, 5.17, 5.12, 5.10, 5.16, and 5.19 μM, respectively. These in vitro results were compared with the reference drug acarbose (IC50 = 200.1 ± 0.15 μM), demonstrating better anti-diabetic inhibitory activity in comparison to the reference drug. The in silico molecular docking study results were consistent with the experimental biological findings, thereby supporting the in vitro pharmaceutical efficacy of the synthesized derivatives.

Naphthyl-functionalized acetamide derivatives: Promising agents for cholinesterase inhibition and antioxidant therapy in Alzheimer’s disease

This study presents the synthesis and characterization of a series of 13 novel acetamides. These were subjected to Ellman’s assay to determine the efficacy of the AChE and BChE inhibitors. Finally, we report their antioxidant activity as an alternative approach for the search for drugs to treat AD. These studies revealed that compounds 1a–1k and 2l–2m were obtained in moderate yield. Four amides (1h, 1j, 1k, and 2l) were selective for one of the enzymes (BChE); thus, those that inhibited BChE were more active than the positive control (galantamine) and showed better IC50 values (3.30–5.03 µM). The theoretical free binding energies calculated by MM-GBSA indicated that all inhibitors were more stable than rivastigmine, and the inhibition mechanisms involved the entire active site: peripheral anionic site, oxyanion hole, acyl-binding pockets, and catalytic site. We examined the cytotoxicity of compounds 1h, 1j, 1k, and 2l in human dermal cells and found that they did not exhibit any toxic effects under the tested conditions. Additionally, these compounds, which also inhibited BChE, displayed mixed inhibition and did not exhibit hemolytic effects on human erythrocytes. Furthermore, the ABTS and DPPH assays indicated that, although none of the compounds showed activity in the DPPH assay, the EC50 values for radical trapping by the ABTS method showed that compounds 1a, 1d, 1e, and 1g had EC50 values lower than 10 µg/mL, indicating their strong radical scavenging capacity. We also report the crystal structures of compounds 1c, 1d, 1f, and 1g, which are found in monoclinic crystal systems.

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents.

Based on the anti-inflammatory and analgesic activity of hydrazone and phthalimide, a new series of hybrid hydrazone and phthalimide pharmacophores was prepared and evaluated as analgesic agents. The designed ligands were synthesized by reaction of the appropriate aldehydes and 2- aminophthalimide. Analgesic, cyclooxygenase inhibitory, and cytostatic activity of prepared compounds were measured. All the tested ligands demonstrated significant analgesic activity. Moreover, compounds 3i and 3h were the most potent ligands in the formalin and writhing tests, respectively. Compounds 3g, 3j, and 3l were the most COX-2 selective ligands and ligand 3e was the most potent COX inhibitor with a 0.79 of COX-2 selectivity ratio. The presence of electron-withdrawing moieties with hydrogen bonding ability at the meta position was found to affect the selectivity efficiently, in which compounds 3g, 3l, and 3k showed high COX-2 selectivity, and compound 3k was the most potent one. The cytostatic activity of selected ligands demonstrated that compounds 3e, 3f, 3h, 3k, and 3m showed good analgesic and COX inhibitory activity and were less toxic than the reference drug. High therapeutic index of these ligands is one of the valuable advantages of these compounds.

Pyrrolidine derivatives as α-amylase and α-glucosidase inhibitors: Design, synthesis, structure-activity relationship (SAR), docking studies and HSA binding

In our pursuit of developing effective inhibitors for the enzymes α-amylase and α-glucosidase, which play a crucial role in carbohydrate metabolism related to type-2 diabetes, we synthesized compounds featuring a pyrrolidine ring. The synthesis involved coupling N-Boc-proline with various aromatic amines, resulting in the formation of distinct N-Boc proline amides. To investigate the influence of the Boc group on enzyme inhibition, the Boc group was subsequently removed. In vitro, testing against α-amylase and α-glucosidase, with metformin and acarbose as reference standards, revealed that the 4-methoxy analogue 3g showed noteworthy inhibitory activity, with IC50 values of 26.24 and 18.04 μg/mL, respectively. Compounds 3a with an IC50 value of 36.32 μg/mL and 3f with an IC50 value of 27.51 μg/mL displayed significant inhibitory activity against α-amylase and α-glucosidase, respectively. The results of molecular docking studies of the most potent pyrrolidine derivatives 3a and 3g with α-amylase and 3f and 3g with α-glucosidase showed good agreement with experimental data. Moreover, compound 3g showed strong binding interactions with HSA having binding constant values of 7.08 × 105 M−1 and 4.77 × 105 M−1 using UV–visible and fluorescence spectrophotometry, respectively.

Exploring Acyl Thiotriazinoindole Based Pharmacophores: Design, Synthesis, and SAR Studies with Molecular Docking and Biological Activity Profiling against Urease, α-amylase, α-glucosidase, Antimicrobial, and Antioxidant Targets.

A diminutive chemical library of acyl thiotriazinoindole (ATTI) based bioactive scaffolds was synthesized, instigated by taking the economical starting material Isatin, through a series of five steps. Isatin was first nitrated followed by the attachment of pentyl moiety via nucleophilic substitution reaction. The obtained compound was reacted with thiosemicarbazide to obtain thiosemicarbazone derivative, which was eventually cyclized using basic conditions in water as solvent. Finally, the reported series was obtained through reaction of nitrated thiotriazinoindole moiety with differently substituted phenacyl bromides. The synthesized compounds were characterized using NMR spectroscopy and elemental analysis. Finally, the synthesized motifs were scrutinized for their potential to impede urease, α-glucosidase, DPPH, and α-amylase. Compound 5h with para cyano group manifested the most pivotal biological activity among all, displaying IC50 values of 29.7 ± 0.8, 20.5 ± 0.5 and 36.8 ± 3.9µM against urease, α-glucosidase, and DPPH assay, respectively. Simultaneously, for α-amylase compound 5g possessing a p-CH3 at phenyl ring unfolded as most active, with calculated IC50 values 90.3 ± 1.1µM. The scaffolds were additionally gauged for their antifungal and antibacterial activity. Among the tested strains, 5d having bromo as substituent exhibited the most potent antibacterial activity, while it also demonstrated the highest potency against Aspergillus fumigatus. Other derivatives 5b, 5e, 5i, and 5j also exhibited dual inhibition against both antibacterial and antifungal strains. The interaction pattern of derivatives clearly displayed their SAR, and their docking scores were correlated with their IC50 values. In molecular docking studies, the importance of interactions like hydrogen bonding was further asserted. The electronic factors of various substituents engendered variety of interactions between the ligands and targets implying their importance in the structures of the synthesized heterocyclic scaffolds. To conclude, the synthesized compounds had satisfactory biological activity against various important targets. Further studies are therefore encouraged by attachment of different substitutions in the structure at various positions to enhance the activity of these compounds.

Synthesis and in vitro evaluation of tetrazole containing 1,5-benzothiazepines as new anticancer, antitubercular, antibacterial, and antifungal agents

Heterocyclic scaffolds have attracted great attention of organic chemists and medicinal chemists, also because of their wide range of synthetic applicability and broad spectrum of biological profile. Therefore, in the present research work, a series of tetrazole containing 1,5-benzothiazepines have been synthesized for evaluation of their biological activities to determine the potential therapeutic profile of these compounds across various medicinal domains. Of the synthesized compounds, five compounds (6f, 8e, 8f, 8g, and 8h) have been screened for anticancer, antitubercular, antibacterial, and antifungal activities. After evaluation of these biological activities, it was found that these compounds possess very limited anticancer activity, moderate antibacterial and antifungal activity, and very strong antitubercular activity, which indicate their great pharmacological applications as subjects for future investigations of novel therapeutic agents for the treatment of tuberculosis.

Synthesis, Characterization, and Antidiabetic Evaluation of N-((5-(3- chloro-4-nitrophenyl)-1,3,4-oxadiazol-2-yl) carbamothioyl) Benzamide Derivatives.

A series of novel N-((5-(3-chloro-4-nitrophenyl)-1,3,4-oxadiazol-2-yl) carbamothioyl) benzamide derivatives (2a-2h) were synthesized and characterized for their potential antidiabetic properties. The synthesis involved multi-step reactions starting from 3-chloro-4-nitrobenzoic acid, and the final compounds were purified by recrystallization. The structures were confirmed using melting points, TLC, FTIR, 1 H-NMR, 13C-NMR, and LC-MS. In-silico pharmacokinetic analysis using SwissADME indicated favorable drug-likeness properties for the synthesized compounds, particularly those with electron-withdrawing substituents. In-vitro assays demonstrated significant α-amylase and α-glucosidase inhibitory activities, with compounds 2a, 2g, and 2h showing the highest potency (IC50 values: 23.19-28.61 µM for α-amylase and 23.25-28.25 µM for α-glucosidase), comparable to the standard drug acarbose. The presence of electron-withdrawing groups enhanced the inhibitory effects, while electron-donating groups reduced efficacy. These findings suggest that the synthesized compounds, particularly 2a, 2g, and 2h, hold promise as effective antidiabetic agents.

Synthesis, spectroscopic characterization, DFT calculations, in silico-ADMET and molecular docking analysis of novel quinoline-substituted 5H-chromeno [2,3-b] pyridine derivatives as antibacterial agents.

A convenient, straightforward, and effective one-step reaction for the synthesis of a three-component compound of biologically relevant novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno[2,3-b] pyridine-3-carbonitrile derivatives was designed and synthesized. The synthesis was developed by the reaction between salicylaldehyde 1, 8-hydroxyquinoline 2, 2-aminopropene-1,1,3-tricarbonitrile 3, and the catalytic amount of triethylamine in ethanol at 78°C. This methodology has many beneficial features, including the use of inexpensive and non-hazardous starting materials, single-flask reactions, optimized reaction conditions, the termination of intermediate isolation, easy workup, reducing organic waste products, being chromatography-free, and decreasing the reaction time along with quantitative yields with high functional group tolerance. A proposed mechanism with supporting experimental data is presented, including 1H NMR, 13C NMR, 2D NMR (HMBC, COSY, HSQC), mass, and IR spectroscopy, which are used to characterize the complete derivatives. All synthesized compounds were evaluated in vitro for their antibacterial activities against Bacillussubtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains via the agar-well diffusion method compared with the reference drug gentamicin. The data indicated that compounds 4A, 4F, 4G, 4J, and 4K consistently demonstrated strong antimicrobial activity against Gram-positive and Gram-negative bacteria. Furthermore, a molecular docking investigation was carried out to gain insight into the binding mode of the most promising compounds via the crystal structure of the S. aureus DNA gyrase complex with ciprofloxacin (PDB ID: 2XCT). Density functional theory (DFT) calculations were performed to determine the various molecular properties of the synthesized novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno [2,3-b] pyridine-3-carbonitrile derivatives (4A-4M). On the basis of the reactive sites explored by the molecular electrostatic potential maps, the antibacterial activities of the compounds were screened.

Furan-Triazine clubbed Schiff base derivatives: Computational insight and empirical precision against A-549 and MDA-MB-468 Carcinoma cells

The purpose of this effort is to generate a range of 1,3,5-triazine substituted furan-2-carbaldehyde Schiff base derivatives (5a-5h) that may be employed as anticancer drugs. The effectiveness of recently synthesised compounds was evaluated in vitro against A-549 lung cancer cell line and MDA-MB-468 breast carcinoma cell line, providing an in-depth evaluation of their possible therapeutic effect on these particular cancer types. Compounds 5e and 5g were found to be the most effective of this series in targeting A-549 lungs cancer cells with IC50 values of 6.33 and 0.31 μM, respectively against the standard drug pictilisib (IC50 1.66 μM), while compounds 5a and 5e were found to be the most promising in targeting MDA-MB-468, with IC50 values of 3.97 and 6.38 μM, respectively, against pictilisib (IC50 3.60 μM). To understand their interaction with the essential proteins involved in the progression of cancer, molecular docking studies were carried out, which gave information about their putative mechanisms of action. Furthermore, molecular dynamics simulations were utilised to analyse the stability and dynamic behaviour of the most active compounds inside the protein binding sites. The study revealed several compounds demonstrating notable anticancer activity, offering encouraging possibilities for their continued development and improvement as novel anticancer medications.

Synthesis and evaluation of the anti-TB activity of novel 7-(2-(4-substituted-phenyl)-4,5-diphenyl-1H-imidazol-1-yl)-4-methyl-2H-chromen-2-one derivatives and their DFT studies for NLO application

A series of novel 7-(2-(4-substituted-phenyl)-4,5-diphenyl-1H-imidazol-1-yl)-4-methyl-2H-chromen-2-one derivatives 5(a-g) have been synthesized and reported as anti-TB activity and non-linear optical applications. The activity results show that compounds 5b, 5c, 5d, 5f, and 5g exhibited excellent efficacy with a MIC value of 3.12 μg/mL, one-fold greater than the reference standard streptomycin (6.26 μg/mL). An in silico molecular docking study was performed against InhA protein and the results were consistent with the experimental results. Computational studies were performed using the DFT method and results reveal that the presence of greater electronegativity atoms increases the HOMO-LUMO energy gap. The NLO properties show that the presence of stronger electron-donating substituents increases the ICT, charge delocalization and β0 values. The NBO analysis shows significant interactions between LP (Lone pair), π* and σ* in compounds account for the high polarization and enhanced NLO activity.