Two sets of diphenyl ether derivatives incorporating five-membered 1,3,4-oxadiazoles, and their open-chain aryl hydrazone analogs were synthesized in good yields. Most of the synthesized compounds showed promising in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Three diphenyl ether derivatives, namely hydrazide 3, oxadiazole 4 and naphthylarylidene 8g exhibited pronounced activity with minimum inhibitory concentrations (MICs) of 0.61, 0.86 and 0.99 μg/mL, respectively compared to triclosan (10 μg/mL) and isoniazid (INH) (0.2 μg/mL). Compounds 3, 4, and 8g showed the InhA reductase enzyme inhibition with higher IC₅₀ values (3.28–4.23 µM) in comparison to triclosan (1.10 µM). Correlation between calculated physicochemical parameters and biological activity has been discussed which justifies a strong correlation with respect to the inhibition of InhA reductase enzyme. Molecular modeling and drug-likeness studies showed good agreement with the obtained biological evaluation. The structural and experimental information concerning these three InhA inhibitors will likely contribute to the lead optimization of new antibiotics for M. tuberculosis.

A novel isatin-thiazole-coumarin hybrid and three isatin-hydantoin hybrids were synthesized and assessed for their α-glucosidase and anticholinesterase inhibitory activities. Moreover, their anticancer properties have been observed against the breast cancer cell lines MCF-7 and MDA-MB-231. The coumarin-containing hybrid exhibited the most potent biological activity across all assays. These hybrids demonstrated significant enzyme inhibition and cytotoxicity, highlighting their potential as multifunctional therapeutic agents for metabolic disorders and breast cancer treatment. This study underscores the value of isatin-based hybrid scaffolds in drug discovery. The synthesized isatin coumarin hybrid 5 demonstrated promising cytotoxic activity against both MCF-7 and MDA-MB-231 breast cancer cell lines, with IC₅₀ values of 10.85 μg mL⁻¹ and 14.45 μg mL⁻¹, respectively. The biological evaluation showed that compound 5 had impressive multi-target activity. It displayed strong anticholinesterase inhibition (IC₅₀ = 0.0998 μg mL⁻¹), effective α-glucosidase inhibition (IC₅₀ = 112 μM), and notable anti-MRSA activity (MIC = 1.3 μg mL⁻¹). Molecular docking backed up these findings by showing good binding interactions with the active sites of the target enzymes. The results indicate that compound 5 is a promising candidate for developing multifunctional agents. It could have potential uses in managing neurodegenerative, metabolic, and infectious diseases.

The search for novel potent anticancer and antimicrobial agents is considered a rapidly advancing field and viewed as a constantly evolving area within medicinal chemistry. In this work, a series of novel spiropyrazoline oxindole scaffolds were synthesized based on domino Knoevenagel–Michael cyclization reactions. These compounds were tested for their in vitro cytotoxic activity against HePG-2 [human hepatocellular carcinoma cell line] and MCF-7 [breast cancer cell line]. Compounds 5a, 5b, and 5d showed potent activity against the HePG-2 cell line. Compound 5a was the most potent one and showed activity against both cell lines, with IC₅₀ (μg mL⁻¹) values of 12.3 and 17.3, respectively, compared to adriamycin, with IC₅₀ (μg mL⁻¹) values of 21.6 and 25.5, respectively. An in silico study, encompassing both molecular docking and MD simulations, highlighted the potential of compounds 5a and 5b as potent therapeutic agents targeting the 4I4T protein, compared to three commercially available drugs, namely, adriamycin, sunitinib, and spirobrassinin. This study demonstrates the importance of spiropyrazoline oxindoles for the development of new and potent cancer treatments. The MD simulations confirmed that compound 5a has a more stable and stronger interaction with the 4I4T protein, making it a promising candidate for further development. An in silico study was conducted to support the experimental results, and another one to show the binding affinity with the PBP2a receptor protein of S. aureus for future research. Compound 4a showed a binding affinity energy of −7.9 kcal mol⁻¹, compared to −6.5 kcal mol⁻¹ for linezolid and −6.3 kcal mol⁻¹ for penicillin.

A straightforward, mild and cost-efficient synthesis of various arylamides in water was accomplished using versatile benzotriazole chemistry. Acylation of various amines was achieved in water at room temperature as well as under microwave irradiation. The developed protocol unfolds the synthesis of amino acid aryl amides, drug conjugates and benzimidazoles. The environmentally friendly synthesis, short reaction time, simple workup, high yields, mild conditions and free of racemization are the key advantages of this protocol.