Biological evaluation of newly synthesized α-benzyl monoxime thiocarbohydrazide derivatives as an antimicrobial and anticancer agent: In vitro screening and ADMET predictions

The current comprehensive study showcases a meticulous synthesis of novel class of α-benzilmonoxime thiocarbohydrazide (BMOTC) derivatives, and manifesting their multifaceted potential as antibacterial, antifungal, and anticancer agents. The synthesis of target compounds was performed in three phases using literature methods. In the first step, benzilmonoxime is synthesized using benzil and hydroxyl amine hydrochloride, followed by benzilmonoxime imine using thiocarbohydrazide. The final stage involves combining BMOTC imine with various aldehydes and ketones. The antibacterial and antifungal activities of the synthesized derivatives against five bacterial panels, both Gram-positive and Gram-negative, and one fungal pathogen have been screened. Twelve of the twenty-four synthetic derivatives showed noteworthy activity; eight derivatives exhibited growth inhibition (GI) >73 % against Acinetobacter baumannii, two exhibited GI >95 % against Escherichia coli, and two exhibited GI >93 % against Candida albicans at concentration 32 μg/mL. Further assessment revealed that two derivatives 5v and 5w, exhibited negligible cytotoxicity towards human embryonic kidney cells (HK-293) and human red blood cells (RBC), signifying their promising safety profile at concentration 32 μg/mL (GI against Candida albicans - 97.51 % and 93.71 % respectively). The synthesized compounds were subjected to in vitro cytostatic activity, where a rigorous scrutiny against a diverse panel of NCI 60 cancer cell lines representing various malignancies was carried out. A total of eleven compounds emerged as promising candidates, demonstrating significant growth percent (GP) at a concentration of 10 µM. Notably, compounds 5d, 5h, and 5x, turned up as standout performers, exhibiting potent anticancer activity across multiple cancer types, including colon, CNS, melanoma, and breast cancers. Of particular interest, compound 5d displayed notable antiproliferative effects against leukemia cancer cell lines RPMI-8226 & SR, while maintaining non-cytotoxicity against the same. Compound 5h showcased activity against ovarian, non-small cell lung, and prostate cancers, without inducing cytotoxic effects. Compound 5x demonstrated remarkable anticancer activity against leukemia and breast cancer cell lines, further bolstered by its non-cytotoxic nature. A compelling aspect of this study is the comparative analysis with the established drug molecule sunitinib, revealing that compounds 5d, 5h, and 5x exhibit superior potency. These findings not only highlight the therapeutic potential of the BMOTC derivatives but also underscore their viability as promising candidates for future drug development endeavours. This study serves as a pivotal step towards harnessing the untapped therapeutic potential of BMOTC derivatives in combating microbial infections and advancing cancer therapy.