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

Convenient route to benzo[1,2,3]selenadiazole–isoxazole hybrids and evaluation of their in vitro cytotoxicity

Ali Oubella, Mourad Fawzi, Abdoullah Bimoussa, Abdellah N’Ait Ousidi, Aziz Auhmani, Abdelkhalek Riahi, Anthony Robert, Larbi El Firdoussi, Hamid Morjani, and Moulay Youssef Ait Itto

Laboratoire de Synthèse Organique et Physico-Chimie Moléculaire, Département de Chimie, Faculté des Sciences, Semlalia, Marrakech, Morocco

E-mail: oubellaali1@gmail.com

Received: 3 August 2021  Accepted: 14 January 2022

Abstract:

A series of novel benzo[1,2,3]selenadiazole–isoxazole hybrid compounds were designed and synthesized from natural (R)-carvone. These derivatives were synthesized from the selenation reaction between the corresponding semicarbazones and selenium dioxide (SeO₂) in the presence of glacial acetic acid as a solvent. The structures of the newly synthesized products were fully characterized by spectroscopic analysis (¹H, ¹³C NMR) and HRMS. All the synthesized compounds were tested in vitro against four human cancer cell lines, fibrosarcoma (HT-1080), lung (A-549) and breast (MCF-7 and MDA-MB-231) carcinoma to evaluate their anticancer activity. Most of the semicarbazones and some of the benzo[1,2,3]selenadiazole–isoxazole hybrids showed interesting cell growth inhibitory activity with IC₅₀ values ranging from 10 to 20 µM. Furthermore, semicarbazone bearing 3-phenylisoxazole nucleus and the benzo[1,2,3]selenadiazole-3-p-chlorophenylisoxazole hybrid exhibited significant antiproliferative activity against HT-1080 cells with IC₅₀ values close to 10.9 ± 1.2 and 18.6 ± 2.6 μM, respectively. Furthermore, the semicarbazone bearing a phenyl group on C3 position of the isoxazole nucleus and the 3-(4-chlorophenyl)-benzo[1,2,3]selenadiazole–isoxazole hybrid had a quite good survival performance against MRC5 cells. The mechanism of action of this latter suggested that it induces apoptosis through caspase-3/7 activation.

Graphical abstract

Keywords: Benzo[1,2,3]selenadiazole; Isoxazole; Anticancer activity; Selenium dioxide; (R)-Carvone

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02083-6

Chemical Papers 76 (5) 2935–2946 (2022)