Docking Study, Synthesis, Characterization and Preliminary Cytotoxic Evaluation of New 1,3,4- Thiadiazole Derivatives

Abstract

Objectives: This study has determined that these newly synthesized analogs hold promise as potential sources of novel anticancer agents for combating breast cancer. Methods: We initiated our research by obtaining the crystal structure of Histone deacetylases (HDACs-8) bound with Vorinostat (SAHA) from the Protein Data Bank (PDB code 4QA0). Subsequently, we conducted docking experiments, which revealed that compounds (V c,s, V d,s, V c,t, and V d,t) exhibited favorable docking scores when compared to the standard. These compounds, synthesized through multi-step procedures involving the reaction of intermediate derivatives (IV c,d) with thiosemicarbazide or semicarbazide, were subjected to confirmation of their chemical structures using FT-IR and 1H NMR analysis. Results: The results of our in-vitro cytotoxicity assay (MTT assay) highlighted that compounds V c,t and V d,t exhibited notable inhibition ratios in the breast cancer cell line (MCF-7), while V c,t displayed similar efficacy in human colon adenocarcinoma (HRT-18) compared to the control drug, Vorinostat (SAHA). Conclusion: Our docking analysis led us to conclude that the C=S moiety demonstrated exceptional binding affinity to the zinc binding group of the HDAC enzyme, establishing multiple interaction modes. This finding suggests the potential of these compounds as valuable candidates in the development of anticancer treatments.