New Benzothiazole-Thiadiazole-Based Ketones as Potential Antiviral and Anticancer Agents: Synthesis, DFT, and Molecular Docking Studies

Various substituted benzothiazole-thiadiazole-based ketones 4a-i and 6a-c were synthesized and characterized by the IR, NMR, and MS spectral data. The DFT study of the synthesized ketones 4 and 6 displayed matched configurations of their HOMO and LUMO, with the exception of the nitrophenyl derivatives, whose HOMO extended over the entire molecule. Meanwhile, the antiproliferative effectiveness of the produced ketones was evaluated against diverse cell lines and compared with the reference drug Erlotinib. The ketones exhibited variable inhibitory effects, for example, the ketone 6a has the most potent activity versus Panc-1 (IC₅₀ = 9.34 ± 0.18 μM), whereas 4i showed proper effectiveness against HepG2 (IC₅₀ = 10.91 ± 0.23 μM), and ketone 4a exhibited strong activity against MCF-7 cells (IC₅₀ = 5.66 ± 0.16 μM). Moreover, the H5N1 antiviral efficacy was assessed via a plaque reduction assay, using amantadine as a reference drug. Ketones 2a, 4e, and 4g displayed 100% inhibition, while ketone 4e has the lowest toxic concentration (TC₅₀ 61 μg/μL). Furthermore, the molecular docking results revealed that ketone 4e had the highest binding score owing to several interactions with amino acids of 1JU6 residues. Finally, SwissADME analysis of the synthesized ketones provides key insights into their pharmacokinetic properties.