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Synthesis, Characterization, and Multidimensional In Silico Evaluation of Novel Etodolac-Based 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents

Tiba M. Hameed, Rafid M. Hashim, S. J. Abed, Raneen Hashim Ridha, O. Al-Mohammed Baqer

Organics · pp. 15–15 · Published 7 Apr 2026

10.3390/org7020015

Abstract

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, 1H-NMR, and 13C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study.

In silico ADME Chemistry In vivo Docking (animal) Computational biology Pharmacology Quantitative structure–activity relationship

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