ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Microwave-assisted synthesis of new 2-aryl and 2-alkylimidazolones and evaluation of their in vitro anticancer activity and their in vivo toxicity on zebrafish embryos

Samar Bou Zeid, Aline Hamade, Fadia Najjar, Francois Carreaux, and Samar Eid

Departments of Biology, Chemistry and Biochemistry, Laboratoire D’Innovation Thérapeutique, Faculty of Sciences II, Lebanese University, Fanar, Lebanon

E-mail: fnajjar@ul.edu.lb

Received: 4 September 2020  Accepted: 30 December 2020

Abstract:

Herein we describe the synthesis of five new 2-aryl and 2-alkylimidazolone derivatives via an effective one-pot synthetic strategy assisted by microwave irradiations which allowed us to access the desired product in a reduced time reaction compared to the thermal heating and a slightly better yield (48% compared to 45%). The new imidazolone derivatives were evaluated for their anticancer activity in vitro against MCF-7, MDA-MB-231 and HepG2 cell lines. The results showed good cytotoxic effects for some of these derivatives on both MCF-7 and HepG2 cell lines in the range of 5.7–11.3 µM. Among the synthesized derivatives, 2ab and 2b showed the strongest activity with IC₅₀ values of 7 and 5.7 µM (MCF-7) and 6.2 and 8.6 µM (HepG2), respectively. The cytotoxic activities of these derivatives were moderate compared to those of doxorubicin. However, this product showed higher toxicity in vivo on the development of zebrafish embryos than the synthesized imidazolones. These derivatives at high concentrations exhibited some morphological abnormalities on the embryos.

Keywords: Imidazolone derivatives; One-pot synthesis; Microwave irradiations; Anticancer activity; Zebrafish embryos

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01502-w

Chemical Papers 75 (6) 2549–2560 (2021)