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

Abstract

Background: Our efforts, focused on the discovery of novel antiproliferative agents, led to the identification of an interesting oxadiazole derivative, MD77. Aim: To complete the studies concerning the antiproliferative profile of MD77 , we developed several new derivatives. Materials and Methods: The substitution pattern around the phenyl rings of this compound was analysed 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 counteract human recombinant topoisomerase II α relaxation activity.