ArticleScientific reports2020
Spirofused tetrahydroisoquinoline-oxindole hybrids as a novel class of fast acting antimalarial agents with multiple modes of action.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 18 citations in OpenAlex.
- Identification of Small-Molecule Inhibitors ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Osteoprotective Effects and In Silico Profiling of Parinari curatellifolia Planch. Ex Benth. (Chrysobalanaceae) Extract on Acute Plasmodium berghei-Compromised Rat Bone.Chemistry & biodiversity · 2026Article
- Recent Advances in Synthetic Isoquinoline-Based Derivatives in Drug Design.Molecules (Basel, Switzerland) · 2025Review
- Cell-Based Progression of Spiroindoline Phenotypic Hits Leads to the Identification of Compounds with Diverging Parasitological Profiles against the Human Malaria ParasiteJournal of medicinal chemistry · 2025Article
- Selective Synthesis of Tetrahydroisoquinoline and Piperidine Scaffolds by Oxidative Ring Opening/Ring Closing Protocols of Substituted Indenes and Cyclopentenes.ChemistryOpen · 2025Article
- Asymptomatic carriage of Plasmodium falciparum in children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio.Malaria journal · 2024Article
- Spirofused Tetrahydroisoquinoline-Oxindole Hybrids (Spiroquindolones) as Potential Multitarget Antimalarial Agents: Preliminary Hit Optimization and Efficacy Evaluation in Mice.Antimicrobial agents and chemotherapy · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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