» Articles » PMID: 9025680

Aminoquinolines That Circumvent Resistance in Plasmodium Falciparum in Vitro

Overview
Specialty Tropical Medicine
Date 1996 Dec 1
PMID 9025680
Citations 36
Authors
Affiliations
Soon will be listed here.
Abstract

Aminoquinoline (AQ) resistance is one of the most important factors in the worldwide resurgence of malaria due to Plasmodium falciparum. We synthesized a series of AQs to define the structure-activity relationships responsible for AQ action against chloroquine-susceptible and -resistant P. falciparum. The AQs with ethyl, propyl, isopropyl, butyl, pentyl, isopentyl (chloroquine), hexyl, octyl, decyl, or dodecyl side chains were equally active against chloroquine-susceptible P. falciparum (50% inhibitory concentrations [IC50s] = 5-15 nM). The AQs with ethyl, propyl, isopropyl, decyl, or dodecyl side chains were also active against chloroquine-, mefloquine- and multiply-resistant P. falciparum (IC50s = 5-20 nM). Verapamil, which enhances the activity of chloroquine against chloroquine-resistant parasites, had no effect on the activity of AQs that were active against resistant parasites. These results indicate that AQs with 2-12 carbon side chains are as active as chloroquine against chloroquine-susceptible P. falciparum, and that AQs with side chains shorter or longer than chloroquine are often active against chloroquine-, mefloquine-, and multiply-resistant P. falciparum.

Citing Articles

Fighting Plasmodium chloroquine resistance with acetylenic chloroquine analogues.

Cortopassi W, Gunderson E, Annunciato Y, Silva A, Dos Santos Ferreira A, Teles C Int J Parasitol Drugs Drug Resist. 2022; 20:121-128.

PMID: 36375339 PMC: 9771834. DOI: 10.1016/j.ijpddr.2022.10.003.


Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro.

Maher S, Vantaux A, Chaumeau V, Chua A, Cooper C, Andolina C Sci Rep. 2021; 11(1):19905.

PMID: 34620901 PMC: 8497498. DOI: 10.1038/s41598-021-99152-9.


Drug susceptibility of in eastern Uganda: a longitudinal phenotypic and genotypic study.

Tumwebaze P, Katairo T, Okitwi M, Byaruhanga O, Orena S, Asua V Lancet Microbe. 2021; 2(9):e441-e449.

PMID: 34553183 PMC: 8454895. DOI: 10.1016/s2666-5247(21)00085-9.


Intrinsic fluorescence properties of antimalarial pyrido[1,2-]benzimidazoles facilitate subcellular accumulation and mechanistic studies in the human malaria parasite .

Korkor C, Garnie L, Amod L, Egan T, Chibale K Org Biomol Chem. 2020; 18(42):8668-8676.

PMID: 33078179 PMC: 7710849. DOI: 10.1039/d0ob01730b.


Unsymmetrical Bisquinolines with High Potency against Malaria.

Liebman K, Burgess S, Gunsaru B, Kelly J, Li Y, Morrill W Molecules. 2020; 25(9).

PMID: 32397659 PMC: 7249153. DOI: 10.3390/molecules25092251.