Evaluation of anticancer activity of some new hybrids of 1,3,4-oxadiazole tethered cinnamamides

• Published in: Journal of molecular structure 2025-02, Vol.1322, p.140438, Article 140438
• Main Authors: Rasras, Anas J., Jaradat, Da'san M.M., Chandrasekaran, Balakumar, Hamadneh, Lama, Younes, Eyad A., Nuwar, Mohammad Abu, Khazaleh, Nasha't, Mahli, Abdo, Al Zubi, Mohammad S.
• Format: Article
• Language: English
• Subjects: 1,3,4-Oxadiazole; Anticancer agents; Cinnamamide; DFT; Molecular docking; Thymidine phosphorylase
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.140438

•A series of novel hybrids of 1,3,4-oxadiazole tethered cinnamamides was synthesized and evaluated of their anticancer activity.•Among the tested compounds, compound 23 showed inhibition against MCF-7 breast cancer cell lines reaching 30.23 %, whereas compound 21 exhibited an inhibition of 30.99 % against prostate cancer cell lines (PC-3).•Structure-activity relationship indicated the influence of electron-withdrawing functional groups on the anticancer activity, positively.•DFT calculations shows correlation between the chemical descriptor values and anti-cancer properties, higher Egap, leading to high chemical hardness leads to increased anticancer activity. A series of novel hybrids of 1,3,4-oxadiazole tethered cinnamamides was synthesized and characterized spectroscopically using 1H NMR, 13C NMR, and HR-MS. The synthesized compounds were screened for their anticancer activity using MTT (in vitro) assay involving different cancer cell lines such as MCF-7, MDA-AMB-231, DU-145, and PC-3. Among the tested compounds, compound 23 showed percentage inhibition against MCF-7 breast cancer cell lines reaching 30.23 %, whereas compound 21 exhibited an inhibition of 30.99 % against prostate cancer cell lines (PC-3). The highly active seven compounds were further assessed to determine IC50 values against MCF-7 and PC-3 cell lines. Of which, compound 8 showed potent inhibition of 1.08 µM. None of the compounds exhibited any cytotoxicity toward normal cells. Structure-activity relationship analysis indicated the influence of electron-withdrawing functional groups on the anticancer activity, positively. This has been further supported by molecular modeling studies such as DFT analysis and molecular docking simulation. Pharmacokinetics ADME properties and drug likeliness are also determined, establishing the compounds druggability. Thus, the synthesized derivatives could be promising leads for further optimization to achieve novel anticancer agents.