| Autor: |
Efange NM; Department of Biochemistry and Molecular Biology, University of Buea, P.O. Box 63, Buea, Cameroon.; Centre Pasteur du Cameroon, Yaoundé, Cameroon., Lobe MMM; Department of Chemistry, University of Buea, P.O. Box 63, Buea, Cameroon., Keumoe R; Centre Pasteur du Cameroon, Yaoundé, Cameroon., Ayong L; Centre Pasteur du Cameroon, Yaoundé, Cameroon. ayong@pasteur-yaounde.org., Efange SMN; Department of Chemistry, University of Buea, P.O. Box 63, Buea, Cameroon. efange.mbua@ubuea.cm. |
| Jazyk: |
angličtina |
| Zdroj: |
Scientific reports [Sci Rep] 2020 Oct 21; Vol. 10 (1), pp. 17932. Date of Electronic Publication: 2020 Oct 21. |
| DOI: |
10.1038/s41598-020-74824-0 |
| Abstrakt: |
Molecular hybridization of privileged scaffolds may generate novel antiplasmodial chemotypes that display superior biological activity and delay drug resistance. In the present study, we describe the in vitro activities and mode of action of 3',4'-dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones, a novel class of spirofused tetrahydroisoquinoline-oxindole hybrids, as novel antimalarial agents. Whole cell phenotypic screening of these compounds identified (14b), subsequently named (±)-moxiquindole, as the most potent compound in the current series with equipotent antiplasmodial activity against both chloroquine sensitive and multidrug resistant parasite strains with good selectivity. The compound was active against all asexual stages of the parasite including inhibition of merozoite egress. Additionally, (±)-moxiquindole exhibited significant inhibitory effects on hemoglobin degradation, and disrupted vacuolar lipid dynamics. Taken together, our data confirm the antiplasmodial activity of (±)-moxiquindole, and identify 3'4'-dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones as a novel class of antimalarial agents with multiple modes of action. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
