A series of novel thiosemicarbazide derivatives (2a-d) were synthesized from 3,5-bis(trifluoromethyl) benzohydrazide (1) and various substituted isothiocyanates. The structures of novel compounds were determined by analytical and spectral (IR, 1H-NMR, and elemental analysis) methods. In silico studies were conducted to determine and evaluate the potential anticancer activity of the compounds. Target-oriented drug design is crucial for cancer therapy for increasing the selectivity and consequently decreasing the adverse effects of anticancer agents. Computer-aided drug design technology enables us to design and develop target-oriented and hence, selective therapeutic agents. We benefited that technology during our drug design process and selected our targets as ATP-dependent enzyme topoisomerase II (Topo II), epidermal growth factor receptor (EGFR) tyrosine kinase domain, carbonic anhydrase IX and tubulin-colchicine: stathmin-like domain complex, which has significant roles in the cancer development process by their biochemical and physiological activities. In the light of the results obtained from in silico studies, the title compounds displayed significant potential activity about possessing the qualification of being multi-target drugs by effecting and hitting a few of the main targets of cancer chemotherapy together and at the same time.
Key words: Thiosemicarbazide, synthesis, computer-aided drug design
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