Garima Pandey

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 synthesised and their in silico and biological evaluations were conducted to explore their antimicrobial potential. To gain deeper mechanistic insight, the synthesised 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.

Coumarins are a class of naturally occurring aromatic compounds with promising medicinal applications due to their broad spectrum of biological effects, including anti‐inflammatory, anticancer, anticoagulant, and antiviral capabilities, because of their favorable drug‐like characteristics, which include high solubility, low molecular weight, excellent bioavailability, and minimum toxicity. Many coumarin derivatives have been extracted from different plant sources in recent years, and their extracts are being used as traditional remedies. Despite their significance, several studies have addressed various aspects of coumarin derivatives, but the current study offers an updated and integrated viewpoint that includes new synthetic methodologies, pharmacological discoveries, and emerging research prospects. This study addresses the knowledge gap and attempts to assist researchers in the design and synthesis of novel coumarin‐based medications for a variety of illnesses, such as cardiovascular, inflammatory, infectious, and oncological conditions, by offering a methodical summary of their medicinal chemistry and clinical uses.

Schizophrenia poses a substantial mental health challenge, affecting 5 individuals per thousand. The prevalence of this serious mental illness emphasizes the imperative need for ongoing research. In this study, authors have explored the therapeutic potential of a library of previously synthesized xanthene analogues by their research group as antagonists of the dopamine D2 receptor (D2R) in the context of neuropsychiatric conditions such as schizophrenia and Parkinson's disease. All the molecules were docked against the dopamine D2 receptor using Auto Dock vina. Based on the binding energy obtained, it can be seen that AR28 shows the best binding affinity (i.e., ‐11.5 kcal/mol) and also forms a stable complex. ADMET experiments assessed pharmacokinetics and safety, while computational models evaluated lipophilicity, solubility, and drug‐likeness. DFT calculations provided insights into electrical characteristics, stability, reactivity, and potential biological activities. From molecular dynamic simulations, it was found that the complexes were stable over time. For AR28 ΔG obtained from MMGBSA was found to be −82.34 kcal/mol. Our findings collectively highlight the promising inhibitory potential of these xanthene analogues against D2R activity, with the results from molecular docking, molecular simulation, ADMET investigations, and DFT simulations offering comprehensive insights into their binding interactions, pharmacokinetic parameters, and electronic properties.