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

• Published in: Chemical papers Vol. 76; no. 5; pp. 2935 - 2946
• Main Authors: Oubella, Ali, Fawzi, Mourad, Bimoussa, Abdoullah, N’Ait Ousidi, Abdellah, Auhmani, Aziz, Riahi, Abdelkhalek, Robert, Anthony, El Firdoussi, Larbi, Morjani, Hamid, Ait Itto, Moulay Youssef
• Format: Journal Article
• Language: English
• Published: Warsaw Versita 01-05-2022
• Subjects: Biochemistry; Biotechnology; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Industrial Chemistry/Chemical Engineering; Materials Science; Medicinal Chemistry; Original Paper; Selenium dioxide; Benzo[1,2,3]selenadiazole; Isoxazole; (; Carvone; Anticancer activity
• ISSN: 0366-6352; 1336-9075; 2585-7290
• DOI: 10.1007/s11696-022-02083-6

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 (SeO
2
) in the presence of glacial acetic acid as a solvent. The structures of the newly synthesized products were fully characterized by spectroscopic analysis (
1
H,
13
C 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 IC
50
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 IC
50
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