Synthesis, Characterization, Antibacterial Activity And Molecular Docking Studies Of Novel Nitrogen Based Indole-2-One Schiff’s Bases

Synthesis of novel antipyrine-azole-S-alkyl derivatives antimicrobial activity, molecular docking, and computational studies

Facile synthesis of pyrimidine substituted-1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives and their antimicrobial activity correlated with molecular docking studies

Design, synthesis, biological assessment and molecular docking studies of some new 2-Thioxo-2,3-dihydropyrimidin-4(1H)-ones as potential anticancer and antibacterial agents

In the present study, ten novel derivatives of dibenzoxepine-11-one, have been synthesized and thoroughly characterized using spectroscopic techniques, including 1H and 13C NMR, FTIR, and HRMS. Density Functional Theory (DFT) calculations were carried out to analyze the geometrical structure and vibrational modes, enabling the identification of the most stable conformation of the lead compound. Time-Dependent DFT (TD-DFT) was employed to investigate the electronic transitions within the UV-Vis spectrum. Molecular docking studies were performed for all derivatives using various target proteins with PDB IDs:IKZN (for E. coli), 1IYL (for C. albicans), and the DNA dodecamer structure (PDB ID: 1BNA). The results revealed favorable binding interactions across all targets. Additionally, molecular dynamics (MD) simulations were conducted for 50 ns using the most promising compound, 7a, confirming the stability of its binding conformation. From in vitro studies, antibacterial activity was assessed for all the synthesized derivatives against Gram-positive strains (B. subtilis, L. rhamnosus) and a Gram-negative strain (E. coli). Compounds 7a, 7b, 7c, 7d, and 7f exhibited strong antibacterial efficacy, with minimum inhibitory concentration (MIC) values of 8 μg ml−1 for E. coli and L. rhamnosus and 16 μg ml−1 for B. subtilis bacterial strains. Additionally, compound 7a exhibited good antifungal activity, with a maximum zone of inhibition of 18 mm against the fungal strain C. albicans. Further UV-Vis absorption and fluorescence quenching studies, conducted for compounds 7a, 7b, and 7e with calf thymus DNA (ct-DNA), suggested a groove-binding interaction. Compound 7a demonstrated the strongest binding affinity, with a binding constant (Kb) of 3.61 × 105 M−1 and a Gibbs free energy change (ΔG) of −31.70 kJ mol−1. Therefore, these novel dibenzoxepine-11-ones derivatives are multifaceted in their action as potential antimicrobial and DNA-binding agents, and will be useful in developing new therapeutics.

The present study was designed to evaluate the antibacterial activity of water, methanol, chloroform and petroleum ether extracts of Psidium guajava and Gymnema sylvestre on Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi by using agar well diffusion method. Both plant extracts showed considerable activity against gram positive and gram negative bacteria. Water extract of Psidium guajava showed good activity against gram positive bacteria and the methanolic extract against gram negative bacteria while chloroform and petroleum ether extracts have only activity against gram positive bacteria but less than water and methanolic extracts which indicated that its polar component have stronger activity against both gram positive and gram negative bacteria than non polar. Gymnema sylvestre extracts also showed activity against both gram positive and gram negative bacteria except water extract which showed no activity against the studied bacteria. The methanolic extract had stronger activity against gram-negative bacteria than chloroform and petroleum ether extracts and had no activity against Salmonella typhi at this concentration but had activity against Escherichia coli but weaker than chloroform and petroleum ether extracts. This indicated that its polar component (methanolic extract) had good activity against gram positive than gram negative bacteria. While chloroform and petroleum ether extracts have stronger activity against gram negative than gram positive bacteria. This indicated that its non-polar components have stronger activity against gram negative bacteria. Keywords: Antibiotic Resistance, Psidium guajava, Gymnema sylvestre, Inhibitory Zone, Plant Extracts, Solvents

In this work a series of hydrazone Schiff base compounds have been synthesized and characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of the target compounds designed to have 3,4,5-trimethoxy in acid hydrazide part and different substituents in the imine part. The antibacterial activity of the synthesized compounds has been studied against two gram positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis) and two gram negative bacteria (Escherichia coli and Klebsiella sp.), while the antifungal activity was studied against candida albicans fungi. The results revealed that most of the synthesized hydrazone derivatives exhibit a moderate antimicrobial activity when compared with the standard drug ampicillin. Molecular docking studies were carried out on the bacteria strain Staphylococcus aureus with target protein DHFR and its complex with trimethoprim (PDB ID: 2W9H).

The leaves and twigs of Viscum album L. (Family: Loranthaceae) were extracted successively with various organic solvents and water. These crude extracts were assessed for antimicrobial activities against three gram positive bacteria that is Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium, five gram negative bacteria that is Escherichia coli,Bordetella bronchisiptica, Salmonella typhi, Pseudomonas aeruginosa, Pseudomonas syringae, one yeast that is Saccharomyces cerevisiae and one filamentous fungusAspergillus flavus by using disc diffusion method. The ethyl acetate, chloroform, ethanol, and methanol crude extracts of selected plant parts had significant antimicrobial activities on both gram positive and gram negative bacteria. The ethyl acetate and methanol crude extracts of leaves and twigs of V. album exhibited prominent activities against gram positive and gram negative bacteria used in comparison to other extracts which had moderate activity against all the tested bacteria. The antimicrobial activities of the crude extracts of the selected plant parts were more active against gram negative bacteria than gram positive bacteria. The standard reference antibiotics, ciprofloxacin (100 um/ml) and nystatin (1500 u/ml) were used as positive control. Key words: Antibacterial, antifungal, disc diffusion, Viscum album, ciprofloxacin, nystatin.

Azofuranone was transformed into a series of pyrazole-based hydrazones with 71–79% yields through hydrazinolysis using hydrazine hydrate at room temperature followed by condensation with selected aromatic aldehydes in refluxing ethanol. The antiproliferative activity of the obtained derivatives was evaluated against MCF-7 (breast) and HCT-116 (colon) cancer cell lines using the MTT assay. Among the tested compounds, the chlorobenzylidene derivative (3a) exhibited the most pronounced cytotoxic activity (IC50 = 6.33 ± 1.3 µM against HCT-116 and IC50 = 8.61 ± 1.6 µM against MCF-7), while the remaining hydrazones also showed moderate to strong effects in both cell models. Computational target predictions suggested possible involvement of kinase-related pathways. Molecular docking studies were performed using CDK2 (PDB ID: 2 A4L) to explore potential binding modes. Compound 3a displayed a favorable docking score compared with the reference ligands and formed hydrogen-bond interactions with key residues within the active site. Molecular dynamics simulations indicated stable ligand–protein interaction patterns over the simulation period. In addition, in silico ADME analysis revealed acceptable physicochemical and pharmacokinetic characteristics, with compound 3a demonstrating the most balanced profile. Overall, the combined biological and computational findings identify compound 3a as a promising scaffold for further optimization in the development of antiproliferative agents.

Kalanchoe pinnata Pers. is one of the famous herbal in Indonesiathat has been used traditionally to treat diarrhea and dysentery. Akinsulire etal., (2007) proved the antibacterial effects of metanolic extract fromKalanchoe pinnata Pers. leaves, and its sensitive to Gram positive andnegative bacteria. Aims of this research are to find out antibacterialactivities of ethyl acetate fraction of methanolic extract from Kalanchoepinnata Pers. leaves to Gram positive bacteria (Staphylococcus aureus,Bacillus subtilis) and Gram negative bacteria (Pseudomonas aeruginosa,Escherichia coli, Salmonella typhi), to determine Minimum InhibitoryConcentration (MIC) of the fraction, and to find out the active chemicalsubstance of the fraction.Methanolic extract of Kalanchoe pinnata Pers. leaves was made byusing maceration method, then the extract was partitioned gradually byusing hexane, chloroform, diethyl ether and ethyl acetate. Ethyl acetatefraction was examinated in vitro according to turbidimetry methods.Concentrations of the fraction were 256, 192, 160, 128, 96, 64, 32 and 16mg/ml. The active chemical substance of the fraction was identified by ThinLayer Chromatography (TLC) method.The result of this research shows the antibacterial activities of ethylacetate fraction of methanolic extract from Kalanchoe pinnata Pers. leavesboth to Gram positive bacteria and Gram negative bacteria. MIC value ofthe fraction to Gram positive bacteria (Staphylococcus aureus, Bacillussubtilis) is 192 mg/ml, and Gram negative bacteria which are Escherichiacoli ATCC 25922 and Pseudomonas aeruginosa is 192 mg/ml, but the MICvalue to Salmonella typhi is 128 mg/ml. TLC identification show that thefraction contains flavonoid. Keywords : Ethyl acetate fraction of methanolic extract from Kalanchoepinnata Pers. leaves, Antibacterial activity, MinimumInhibitory Concentration (MIC), Flavonoid

A new series of 5-sustituted-3-((2-(4-nitrophenyl) Thiazol-4-yl) Imino)-1-(substituted-1-ylmethyl) Indolin-2-one derivatives (3a-3l) are synthesized by conventional method. All synthesized compounds were characterized via IR, 1H-NMR, 13C-NMR and MASS spectral analysis. Compounds were evaluated for their anticancer activity against MCF-7 cell lines and antibacterial activity against Staphylococcus aureus, Bacillus subtilis, E. Coli and Salmonella paratyphi. These results indicated that compound 3a, 3e, 3f and 3j showed good activity compared to the standard drug. Synthesized target molecules exhibited anticancer activity against breast cancer cell lines with IC50 values of range from 60.21. to 130.21 μg. Compound 3c (60.21μg) showed good activity compared with doxorubicin. Compounds were subjected to molecular docking studies with estrogen receptor (ER) epidermal growth factor receptor (EGFR) with PDB ID:3ERT. Among the docked ligands, compound 3a and 3e reported highest docking score (-8.512, -6.869) with glide binding energy (-43.785, -24.187).

A series of new deoxybenzoin based bis 1,2,3‐triazole analogues were synthesized and reported in the present communication. Synthesis of analogues were accomplished by a convenient 3 step protocol incorporating Friedel craft acetylation, propargylation and copper‐catalyzed click chemistry in final step to afford 1,2,3‐triazole moiety. The title compounds were screened for antimicrobial activity against two gram positive bacteria viz. S. aureus, B. cereus and two gram negative bacteria viz. E. coli, P. aeruginosa , and three fungus viz. C. albicans, A. niger, A. flavus strains. Compound containing 4‐fluoro substitution (7a) showed slightly superior in‐vitro antimicrobial activity than reference drugs Ciprofloxacin and Fluconazole . SAR of developed hybrids with reference to antimicrobial activity was predicted and presented. In‐silico bioactivity is investigated by molecular docking studies against the crystal structures of glucosamine‐6‐phospate synthase (PDB ID: 2VF5) and secreted aspartic proteinase (PDB ID: 2QZW) which endorsed good binding interactions.

In the present work, novel Schiff base macrocyclic Zn(II) complexes [Zn(N8O4MacL1)Cl2–Zn(N8O4MacL3)Cl2] were synthesized by the reaction of ZnCl2 and macrocyclic ligands (N8O4MacL1–N8O4MacL3) derived from the condensation of ligand (L) and dicarboxylic acids [HOOC‐(CH2)n‐COOH]. The structural confirmation of the newly synthesized compounds was accomplished through various analytical techniques, including elemental analysis, infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), UV–visible spectroscopy, and powder X‐ray diffraction (XRD) studies. The spectral data provided evidence that the macrocyclic ligands acted as tetradentate ligands, forming coordination bonds with Zn(II) ions through the nitrogen atom of the imine (>C=N) group. The coordination complexes exhibited an octahedral geometry around the zinc ion, with two chloro groups covalently attached. Density functional theory (DFT) studies of the synthesized Schiff base macrocyclic compounds were carried out to determine their structural and electronic properties. The antimicrobial potential of the macrocyclic compounds was examined against a panel of pathogenic microbes, including four bacterial strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Xanthomonas campestris) and two fungal strains (Fusarium oxysporum and Candida albicans). Then, the newly synthesized Schiff based macrocyclic compounds were evaluated for their anti‐inflammatory activity using an egg albumin method. The synthesized compounds were subjected to further evaluation to assess their potential as anticancer agents against MCF‐7 (human breast adenocarcinoma cell line), HCT‐116 (human colon cancer cell line), and A549 (human alveolar adenocarcinoma epithelial cell line). In addition, molecular docking studies were conducted to explore the potential interactions between the synthesized compounds and the target proteins VEGFR2 (PDB ID 1YWN), EGFR (PDB ID 1M17), and DNA gyrase B (PDB ID 4URO). It was found that there was a high correlation between the experimental results and the docking calculations.

2, 3, 5-Trisubstituted-1, 3, 4-Oxadiazol-3-(2H)-yl methanone derivatives are synthesized and characterized by spectral methods such as IR, 1H NMR, [Formula: see text]C NMR and MS. The molecular docking study was conducted with assorted bacterial and fungal target proteins (PDB Id: 2ZCO, 1SNN, 1CVU, 3OSV, 6IV7 and 7BLY) to study the binding interactions of synthesized compounds. Scaffold 2[Formula: see text] exhibited the best docking scores of –10.5, –10.0, –9.5 and –10.5 kcal/mol against target proteins 1CVU, 2ZCO, 3OSV and 7BLY, respectively. Further, synthesized analogs showed good to moderate anti-bacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Plasmodium aeruginosa; and anti-fungal activity against Aspergillus Niger and Candida albicans. Remarkably, 2[Formula: see text] and 2[Formula: see text] showed auspicious anti-fungal and anti-bacterial activity compared to other molecules. The DFT study was carried out at the level of B3LYP/6-31G (s) to obtain the optimized geometry of molecules, frontier molecular orbital energies, molecular electrostatic potential plots and global reactivity parameters ([Formula: see text] and [Formula: see text]) to explore their structural and electronic features. Compound 2[Formula: see text] exhibited the highest reactivity ([Formula: see text]: 1.454 eV) and compound 2[Formula: see text] exhibited the lowest toxicity ([Formula: see text]: 1.401 eV) among all analogs. Overall, these findings indicate that compounds 2[Formula: see text], 2[Formula: see text] and 2[Formula: see text] would be prominent intrants for further studies concerning research and development as they exhibit good anti-microbial activity, best docking scores and favorable [Formula: see text], [Formula: see text] and [Formula: see text] parameters.

Objective: The objective of the study is to design novel isoxazole derivatives, predicting their interactions with the selected target proteins and determining the ADMET properties of potent molecules using recent computational methods.
 Methods: With the intent to discover potent novel antibacterial, we have designed a set of compounds containing the isoxazole nucleus by using software tools like Discovery studios, PyRx, PyMOL, SWISSPDB. ADMET studies were carried out by using SWISS ADMET and pkCSM. Molecular docking studies were carried out on the target proteins of both gram-positive and gram negative bacteria in order to assesses binding affinity for the proteins.
 Results: Designed scaffold was designed by Benzene Derivatives Tethered with 5(4-chloro-3-nitro phenyl-1-yl) isoxazole. All the derivatives were docked against the three proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), The compound JJC3F has shown best binding score against DNA ligase, sterol demethylase protein. Further, compound JJC3A has shown a better binding affinity towards topoisomerase than the standard drugs.
 Conclusion: Molecular Docking study indicates that isoxazole derivatives may be effective inhibitors for the different microbial proteins. Additionally, in silico ADMET studies predicts drug-like features. Hence, these compounds may be considered as leads and further investigation of their analogues may help in development of novel drugs for the treatment of microbial diseases.

We report an efficient approach for the synthesis of a series of 2H-chromene-fused-thiazolo-triazole derivatives. This method enables the synthesis of the desired compounds through a multicomponent cascade of C–N and C–S bond formation. The synthesized compounds were thoroughly characterized by 1H NMR, 13C NMR, HRMS, and single-crystal XRD. The anticancer results showed that in the MCF-7 cell line, all tested compounds exhibited better activity than the other two cancer cell lines (MDA-MB-231 and A549). Compounds 4f, 4h and 4i showed significant cytotoxicity against the MCF-7 cell line compared to Doxorubicin. Additionally, in vitro antibacterial activities were evaluated against E. coli (PDB ID: 3G7E) and S. aureus (PDB ID: 3G7B), where compounds 4a, 4e, and 4i showed the highest potency compared to Gentamicin. Molecular docking studies further supported these findings, indicating the strong binding affinities of the active compounds towards the selected protein targets. FMO analysis based on global reactivity parameters indicated that compounds 4a, 4e, 4f, 4h and 4i exhibited high stability. Additionally, MEP plots revealed that these compounds exhibited a strong electrophilic reaction potential. In addition, ADMET predictions indicated favorable physicochemical and pharmacokinetic properties of these potent compounds. Overall, compounds 4a, 4e, 4f, 4h and 4i were identified as promising dual anticancer and antibacterial inhibitors for future drug discovery.