In vitro drug interaction of ionophores with artemisinin and chloroquine against Plasmodium falciparum 3D7 blood-stage infection

Bibliographic Details
Title: In vitro drug interaction of ionophores with artemisinin and chloroquine against Plasmodium falciparum 3D7 blood-stage infection
Authors: Vinoth Rajendran, Keerthana Gurukkalot
Source: Frontiers in Drug Discovery, Vol 3 (2023)
Publisher Information: Frontiers Media S.A., 2023.
Publication Year: 2023
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: ionophores, drug-interaction, isobologram, P. falciparum, antimalarials, Therapeutics. Pharmacology, RM1-950
More Details: The prevalence of clinical resistance of P. falciparum towards artemisinin and its partner drugs has significantly hampered malarial chemotherapy. To circumvent this situation, identifying a new class of partner drugs with significant anti-malarial efficacy and multi-stage activity can slow the development of resistance. This study demonstrates the potential interactions of carboxylic ionophores such as monensin (MON), maduramicin (MAD) or salinomycin (SAL) with standard antimalarial drugs artemisinin (ART) or chloroquine (CQ). The in vitro drug interactions were studied in P. falciparum 3D7 strain by a growth inhibition SYBR green 1 assay. The asynchronized parasites were exposed for 48 h in the presence of varying proportions of two drug concentrations using the modified fixed-ratio isobologram method. We determined the growth inhibition response and the sums of the fractional inhibitory concentrations (Ī£FICs) of the following drug combinations (4:1, 3:2, 2:3, 1:4) and (1:1, 1:3, 3:1) were calculated for 50% inhibitory concentrations (IC50s). Combining artemisinin with monensin, maduramicin, or salinomycin showed significant additive interaction. A combination of chloroquine with monensin, maduramicin, or salinomycin showed slight synergism to additive interaction. None of the drug combinations displayed an antagonistic effect indicating ionophores usage in combination therapy to treat drug-resistant malarial infections.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2674-0338
Relation: https://www.frontiersin.org/articles/10.3389/fddsv.2023.1257698/full; https://doaj.org/toc/2674-0338
DOI: 10.3389/fddsv.2023.1257698
Access URL: https://doaj.org/article/13d02c9ad9ad446796ff8658d2130ebb
Accession Number: edsdoj.13d02c9ad9ad446796ff8658d2130ebb
Database: Directory of Open Access Journals
More Details
ISSN:26740338
DOI:10.3389/fddsv.2023.1257698
Published in:Frontiers in Drug Discovery
Language:English