Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity

Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity Научная публикация

Журнал

ChemMedChem
ISSN: 1860-7179 , E-ISSN: 1860-7187

Вых. Данные

Год: 2018, Том: 13, Номер: 9, Страницы: 902-908 Страниц : 7 DOI: 10.1002/cmdc.201700804

Авторы

Coghi Paolo ¹ , Yaremenko Ivan A. ^2,3,4 , Prommana Parichat ⁵ , Radulov Peter S. ^2,4 , Syroeshkin Mikhail A. ⁴ , Wu Yu Jun ¹ , Gao Jia Ying ¹ , Gordillo Floria M. ¹ , Mok Simon ¹ , Wong Vincent Kam Wai ¹ , Uthaipibull Chairat ⁵ , Terent'ev Alexander O. ^2,3,4

Организации

1	State Key Laboratory of Quality Research in Chinese Medicine; Macau University of Science and Technology; Avenida Wai Long, Taipa Macau China
2	All Russian Research Institute for Phytopathology; 143050 B. Vyazyomy Moscow Region Russia
3	Faculty of Chemical and Pharmaceutical Technology and Biomedical Products; D.I. Mendeleev University of Chemical Technology of Russia; 9 Miusskaya Square Moscow 125047 Russia
4	N.D. Zelinsky Institute of Organic Chemistry; Russian Academy of Sciences; Leninsky Prospect 47 Moscow 119991 Russian Federation
5	National Center for Genetic Engineering and Biotechnology (BIOTEC); National Science and Technology Development Agency (NSTDA); 113 Thailand Science Park Pathum Thani 12120 Thailand

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 capacity–activity. Our findings offer a new source of antimalarial and anticancer agents through structural modification of peroxide

Coghi P. , Yaremenko I.A. , Prommana P. , Radulov P.S. , Syroeshkin M.A. , Wu Y.J. , Gao J.Y. , Gordillo F.M. , Mok S. , Wong V.K.W. , Uthaipibull C. , Terent'ev A.O.
Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed Antimalarial Activity
ChemMedChem. 2018. V.13. N9. P.902-908. DOI: 10.1002/cmdc.201700804 WOS Scopus OpenAlex

Web of science:	WOS:000431626300004
Scopus:	2-s2.0-85046543665
OpenAlex:	W2792032937

БД	Цитирований
OpenAlex	56
Scopus	50
Web of science	52