Amide-functionalized cholic acid hybrids: design, bioactivity, and computational analysis

Pyrene‐linked heterocyclic pyrazoles: Synthesis, antimicrobial screening, and in silico molecular insights

Abstract A library of structurally diverse pyrene‐linked pyrazole derivatives was designed and synthesized, and their antimicrobial properties along with molecular interaction behavior were systematically investigated. The target compounds were efficiently prepared through a straightforward synthetic approach and fully characterized using standard spectroscopic techniques, confirming the formation of the desired heterocyclic framework. Biological evaluation against selected Gram‐positive, Gram‐negative, and fungal strains showed noticeable differences in activity across the series, indicating a strong dependence on the nature and position of substituents as well as their electronic characteristics. Notably, compound 4h emerged as the most active derivative, exhibiting significant antibacterial effects with inhibition zones of approximately 38 mm against Staphylococcus aureus and 29 mm against Proteus vulgaris, demonstrating broad‐spectrum potential. To better understand these results, molecular docking studies were carried out against the Escherichia coli FabB enzyme. Compound 4 h showed the most favorable binding energy (ΔG = −8.9 kcal/mol), supported by stable hydrogen bonding and hydrophobic interactions within the enzyme's active site. In silico analysis also revealed a cLogP value of 7.3390, indicating suitable lipophilicity consistent with drug‐like behavior. In summary, the integration of experimental antimicrobial assessment with computational studies supports the pyrene–pyrazole framework as a promising scaffold for the further development of effective antimicrobial agents.

Pyrazole-Triazole Schiff Bases: Hybrid Molecular Frameworks with Promising Antimicrobial Activity

Development of novel Schiff Base-triazole hybrids with potent antimicrobial agent: Design, synthesis, in-silico and biological evaluation.

The rise of microbes resistant to nearly all classes of antimicrobial drugs has become a severe public health problem in recent years. In this study, a new series of Schiff-base triazole hybrid derivatives was designed and synthesized and their in silico and biological evaluations were conducted to explore their antimicrobial potential. To gain deeper mechanistic insight, the synthesized compounds were subjected to a comprehensive computational workflow that included molecular docking, ADME profiling, DFT calculations, and MD simulations. Molecular docking studies revealed promising binding affinities ranging from -7.00 to -10.8 kcal/mol, placing these compounds on par with clinically established reference drugs in terms of target engagement. Among the series, compound 6j emerged as electronically favourable, exhibiting the lowest HOMO-LUMO energy gap (-0.15163 Hartree) as determined by DFT analysis, a characteristic often associated with enhanced chemical reactivity and biological interaction potential. The dynamic behaviour of the most promising protein-ligand complexes was further interrogated through 100 ns MD simulations, which confirmed robust structural stability throughout the simulation trajectory. Complementing these findings, ADME profiling established that the compounds fulfil the criteria outlined by Lipinski's Rule of Five, underscoring their suitability as orally bioavailable drug candidates. On the biological front, in vitro antimicrobial evaluation against a panel of clinically relevant bacterial and fungal strains yielded encouraging results. Compound 6j demonstrated meaningful antifungal activity, with MIC values spanning 500-1000 μg/mL, while compound 6d stood out for its potent antibacterial performance, achieving an MIC of 500 μg/mL. Collectively, these findings position Schiff-base triazole hybrids as structurally versatile and biologically promising scaffolds, warranting accelerated pharmacological exploration toward the development of next-generation antimicrobial therapeutics.

Green Synthesis, Molecular Modelling, and ADME Evaluation of Functionalized Pyridine Derivatives as Potential SARS-CoV-2 Inhibitors

Design, Synthesis and Molecular Docking-Based Evaluation of Piperazine-Linked Triazine Derivatives as Antioxidant Agents

Oxidative stress is a key driver of the pathogenesis of numerous chronic inflammatory and metabolic diseases emphasizing the requirement for the development of potent and selective antioxidant therapeutics. In present study, a series of novel piperazine-linked 1,3,5-triazine derivatives (6a-h) was rationally designed, synthesised and evaluated for antioxidant activity using integrated computational and experimental approaches. Molecular docking studies were carried out against myeloperoxidase (MPO; PDB ID: 1DNU), a heme-containing enzyme involved in reactive oxygen species (ROS) generation, to examine ligand–protein interactions and binding affinities. The synthesized compounds exhibited binding energies ranging from -3.816 to -4.987 kcal/mol. Among them, compound 6f, bearing a para-fluorophenyl substituent, shows the highest binding affinity (-4.987 kcal/mol). The enhanced binding was attributed to the formation of two hydrogen bonds with ARG27 and LEU97 and exceeded the binding energy of the reference antioxidant, ascorbic acid (-4.690 kcal/mol). The antioxidant potential was assessed by the DPPH free radical scavenging assay. Compound 6f displayed the strongest activity with an IC50 value of 14.15 ± 0.14 µM, which was comparable to that of ascorbic acid (IC50 = 14.06 ± 0.18 µM). Structure-activity relationship analysis indicated that the electron-withdrawing substituents at the para-position of aryl ring, together with nitrogen-containing heteroaromatic moieties, improve both binding affinity and free radical scavenging activity. The results identify piperazine-linked 1,3,5-triazine derivatives as promising antioxidant scaffolds and provide a strong basis for future myeloperoxidase inhibition studies and in vivo pharmacological evaluation.

Synthesis, molecular docking and preliminary anticancer activity of product-C as a hybrid compound against PI3K

The present work describes the synthesis, molecular docking, and preliminary anticancer evaluation of a hybrid compound, product- C composed of a fluorinated sulfur heterocyclic core and an adamantane moiety. The synthesis method was designed to tune the electronic, lipophilic and structural properties of the compound through the introduction of CF₃, F and Cl functional groups, which are well known for the improving metabolic stability, physicochemical properties and drug-likeness. The structure of the synthesized compound was confirmed by 1 H and 13 C nuclear magnetic resonance (NMR) spectra. Molecular docking against phosphoinositide 3-kinase (PI3K), a protein target implicated in multiple cancers, showed that product- C exhibited a binding affinity of -10.6 kcal/mol, suggesting favorable interaction with the target. In parallel, the SRB (Sulforhodamine B) assay was used to evaluate the cytotoxicity of product- C toward PANC-1 cells. Preliminary results showed cell viabilities of 98.86% and 95.55% after exposure to 10 μM and 100 μM of product- C , respectively. These findings indicate that product- C displays low cytotoxicity toward PANC-1 cells under the tested conditions; however, they do not by themselves demonstrate marked antiproliferative activity.