Multicomponent and 1,3-dipolar cycloaddition synthesis of triazole- and isoxazole-acridinedione/xanthenedione heterocyclic hybrids: Cytotoxic effects on human cancer cells

Author links open overlay panelAbdelkaderNaouri^abcAmarDjemoui^abMouhamad RidhaOuahrani^dMokhtar BoualemLahrech^bNajetLemouari^cDjenisa H.A.Rocha^efgHélioAlbuquerque^eRicardo F.Mendes^fFilipe A.Almeida Paz^fLuisa A.Helguero^gKhaldounBachari^cOualidTalhi^ceArtur M.S.Silva^e

Abstract

A new series of diverse 1,2,3-triazole-acridinedione/xanthenedione and 1,2-isoxazole-acridinedione/xanthenedione heterocyclic hybrids have been synthesized via 1,3-dipolar coupling reaction of N/O-substituted-acridinedione-alkyne or O-substituted-xanthenedione-alkyne substrates with various aromatic azides or oximes. In all cases, the cycloaddition is totally regioselective. The chemical structures of the synthesized compounds are determined using 2D NMR and are further confirmed by single-crystal X-ray diffraction analysis. Preliminary in vitro cytotoxic assays on two human breast cancer cell lines (MDA-MB-231, T47-D) and one prostate cancer cell line (PC3) are performed on some selected compounds. The most active O-1,2,3-triazole-xanthenedione hybrid displays the best cytotoxicity effects with IC₅₀ ≤ 20 μM in breast cancer and IC₅₀ = 10 μM in prostate cancer cell lines.