Novel Isoniazid–Based 1,3,4‐Oxadiazole–Fatty Acid Hybrids: Synthesis, In Vitro Biological Activity and In Silico ADME/Tox Predictions

Cancer and multidrug-resistant (MDR) bacterial infections are pressing global health concerns that demand continuous studies on new bioactive compounds. With a view to create new bioactives, the present study reports on the design and synthesis of novel fatty acid derivatives containing oxadiazole moiety and isoniazid in a molecular entity. The structures of the synthesized compounds were confirmed through nuclear magnetic resonance (NMR), infrared (IR) and mass spectrometry. Anticancer screening revealed that compounds 7b and 7e demonstrated notable cytotoxic activity, particularly against the B16-F10 cell line. Compound 7b exhibited the most potent activity with an IC₅₀ of 7.3 ± 0.8 µM in cancer cells and 18.4 ± 0.2 µM in normal cells, indicating a promising selectivity profile. The synthesized derivatives also displayed moderate antibacterial and antifungal effects in preliminary screening. Computational evaluations supported their drug-like physicochemical properties and favourable pharmacokinetics, whereas Toxicity Prediction by Computer Assisted Technology (TOPKAT) (a robust quantitative structure-toxicity relationship [QSTR]-based toxicity prediction tool) indicated promising safety profiles across multiple endpoints, such as mutagenicity and carcinogenicity. Together, these findings highlight these isoniazid-oxadiazole-fatty acid hybrids as promising dual-acting therapeutic candidates, warranting further development.