New 1,3,4-oxadiazole derivatives as potential anticancer agents against esophageal cancer: Synthesis, biological evaluation, molecular docking, and density functional theory study

Abstract

Four new 1,3,4-oxadiazole derivatives (L1-L4) were synthesized through a four-step synthetic pathway involving hydrazide formation, cyclization to the 1,3,4-oxadiazole ring, hydrazination, and hydrazone formation by condensation with appropriate aldehydes. Their anticancer potential against esophageal adenocarcinoma (SKG-T4) cells was investigated using molecular docking and MTT assay. Molecular docking studies using epidermal growth factor receptor (Protein Data Bank: 4HJO and 1M17) showed that L2 exhibited the strongest binding affinity toward 4HJO (-8.05 kcal/moL), exceeding that of Erlotinib (-7.67 kcal/moL), while L3 displayed the best performance among the synthesized compounds with 1M17 (-6.61 kcal/moL). Density functional theory calculations revealed the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps ranging from 3.83 to 3.94 eV, indicating favorable electronic properties. MTT assays demonstrated concentration-dependent cytotoxicity of L2 and L3 against SKG-T4 cells, IC50 of L3 = 241.7 μg/mL, whereas no IC50 could be determined for L2 within the tested concentration range. Overall, the results identified L2 and L3 as promising 1,3,4-oxadiazole-based candidates for further development as anticancer agents against esophageal cancer.. KEYWORDS :Oxadiazole derivatives, Esophageal carcinoma, Epidermal growth factor receptor inhibition, Molecular docking, Anticancer activity.