Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity

ChemMedChem
Paolo CoghiAlexander O Terent'ev

Abstract

Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4-trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in vitro antimalarial activity against Plasmodium falciparum (3D7) and for their cytotoxic activities against immortalized human normal fibroblast (CCD19Lu), liver (LO2 ), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest cytotoxicity on HepG2 (IC50 =0.19-0.59 μm), and some of these compounds selectively targeted liver cancer (selectivity index values for compounds 13 a and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher than those of paclitaxel, artemisinin, and artesunic acid. In contrast some ozonides showed only moderate antimalarial activity against the chloroquine-sensitive 3D7 strain of P. falciparum (IC50 from 2.76 to 24.2 μm; 12 b, IC50 =2.76 μm; 13 a, IC50 =20.14 μm; 14 a, IC50 =6.32 μm). These results suggest that these derivatives have divergent mechanisms of action against cancer cells and malaria-infected cells. A cyclic voltammetry study of the peroxides was performed, but most of the compounds did not show direct correlation in oxidative ...Continue Reading

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Citations

Aug 1, 2018·Angewandte Chemie·Mikhail A SyroeshkinIgor V Alabugin
Oct 30, 2018·Anti-cancer Agents in Medicinal Chemistry·Angelina M FuzerMarcia R Cominetti
Apr 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivan A YaremenkoAlexander O Terent'ev
Apr 16, 2020·Chemistry & Biodiversity·Isabel V AntolínezRicardo T Fujiwara
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nataliya MakhmudiyarovaUsein Dzhemilev
Dec 4, 2020·Fitoterapia·Carolyne ChepkiruiAbiy Yenesew
Mar 11, 2020·ChemMedChem·Ivan A YaremenkoAlexander O Terent'ev
Feb 22, 2021·Bioorganic Chemistry·Saad ShaabanFardous F El-Senduny
Jul 16, 2021·Chemical Society Reviews·Igor V AlabuginMohammad Ali Zolfigol

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