Unravelling the Antiproliferative Activity of 1,2,5-oxadiazole Derivatives

Abstract

Aim: To develop several new derivatives aimed to complete the studies concerning the antiproliferative profile of the oxadiazole derivative MD77.

Materials and methods: The substitution pattern around the phenyl rings of this compound was analyzed through the synthesis of positional isomers and of analogues bearing different substituents at the para positions (2-12).

Results: The results of the antiproliferative activity of these derivatives versus HCT-116 and HeLa cancer cell lines shed light on the effects of the presence, nature and position of such substituents. Notably, derivative 4, a regioisomer of 1 in which the substituents at the para positions of the phenyl rings were inverted, showed the best antiproliferative profile, exhibiting a significant activity also against MCF7 and MDA-MB 468 cancer cell lines.

Conclusion: Preliminary results showed the ability of compound 4 to reduce the viability of cancer cells by counteracting human recombinant topoisomerase II α relaxation activity.

Keywords: Furazane; HCT-116; HeLa; MCF-7; MDA-MB 468; cytotoxicity; topoisomerase II.