Synthesis and theoretical evaluation of a benzylthio-substituted 1,3,4-oxadiazole: Structural characterization and anticancer assessment in Dalton's lymphoma

Abstract

Cancer is characterized by uncontrolled proliferation and spread of abnormal cells, leading to disruption of physiological processes and organ damage. In this work, we report the synthesis, structural characterization, photophysical properties, and anticancer evaluation of 2-(5-(benzylthio)-1,3,4-oxadiazol-2-yl)phenol (Bzop). The compound was synthesized via cyclization of potassium N′-(2-hydroxybenzoyl)hydrazinecarbodithioate with benzyl chloride and characterized by elemental analysis, UV–vis, FT-IR, NMR, and single-crystal X-ray diffraction (SC-XRD). Crystallographic studies revealed a monoclinic system with space group P2₁/c, stabilized by weak intermolecular C-H⋯S, C-H⋯O, and O-H⋯N interactions. Hirshfeld surface analysis and fingerprint plots further confirmed these interactions. DFT calculations supported experimental observations, with a HOMO–LUMO energy gap of 4.04 eV, indicating a relatively soft molecular character and high reactivity. Compound Bzop is fluorescent and exhibits emission maxima at 425 nm upon excitation at 320 nm. The anticancer activity of Bzop was assessed against Dalton's lymphoma (DL) cells using in vitro assays. Bzop exhibited significant antiproliferative activity (IC50 = 49 ± 2.6 µM) and induced hallmark features of apoptosis, including elevated ROS generation, disruption of mitochondrial membrane potential (JC-1 staining), chromatin condensation, and nuclear fragmentation. In addition, apoptosis is confirmed by Annexin-V and PI staining. Overall, this study demonstrates that Bzop is a promising oxadiazole-based scaffold in anticancer drug discovery, warranting further in vivo and mechanistic investigations.