Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors

Tarek A Yousef; Abdulrahman G Alhamzani; Mortaga M Abou-Krisha; G Kanthimathi; M S Raghu; K Yogesh Kumar; M K Prashanth; Byong-Hun Jeon

doi:10.1016/j.heliyon.2023.e13460

Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors

Heliyon. 2023 Feb 8;9(2):e13460. doi: 10.1016/j.heliyon.2023.e13460. eCollection 2023 Feb.

Authors

Tarek A Yousef^{1

2}, Abdulrahman G Alhamzani¹, Mortaga M Abou-Krisha^{1

3}, G Kanthimathi⁴, M S Raghu⁵, K Yogesh Kumar⁶, M K Prashanth⁷, Byong-Hun Jeon⁸

Affiliations

¹ College of Science, Chemistry Department, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi Arabia.
² Department of Toxic and Narcotic Drug, Forensic Medicine, Mansoura Laboratory, Medicolegal Organization, Ministry of Justice, Egypt.
³ Department of Chemistry, South Valley University, Qena, 83523, Egypt.
⁴ Department of Chemistry, Ramco Institute of Technology, Rajapalayam, Tamilnadu, 626117, India.
⁵ Department of Chemistry, New Horizon College of Engineering, Bengaluru 560 103, India.
⁶ Department of Chemistry, Faculty of Engineering and Technology, Jain University, Ramanagara, 562 112, India.
⁷ Department of Chemistry, B N M Institute of Technology, Bengaluru 560 070, India.
⁸ Department of Earth Resources and Environmental Engineering, Hanyang University, 222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Abstract

The current study reports on the synthesis and anticancer efficacy of novel oxadiazole derivatives (8a-f) as tubulin polymerization inhibitors. NMR, mass, and elemental studies were used to confirm the newly produced compounds. In contrast to the conventional medicine colchicine, compounds 8e and 8f demonstrated stronger sensitivity and improved IC₅₀ values in the range of 3.19-8.21 μM against breast MCF-7, colorectal HCT116, and liver HepG2 cancer cell lines. The target compounds were tested for enzymatic activity against the tubulin enzyme. Compounds 8e and 8f were shown to have the most effective inhibitory action among the new compounds, with IC₅₀ values of 7.95 and 9.81 nM, respectively. As compared to the reference drug, molecular docking investigations of the developed compounds revealed the crucial hydrogen bonding in addition to the hydrophobic interaction at the binding site, assisting in the prediction of the structural requirements for the found anticancer activity. These findings indicate that the 1,3,4-oxadizole scaffold has the potential for future research into new anticancer medicines.

Keywords: 1,3,4-Oxadiazole; Anticancer; Molecular docking; Tubulin inhibitors.