ArticleScientific reports2019
Antimalarial Quinoline Drugs Inhibit β-Hematin and Increase Free Hemin Catalyzing Peroxidative Reactions and Inhibition of Cysteine Proteases.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 95 citations in OpenAlex.
- Identification, Structure-Activity Relationship (SAR), and Biological Evaluation of New Chemical Series as Malaria ParasiteACS omega · 2026Article
- Searching for new candidates for antimalarial therapy: physicochemical and in vitro evaluation of gold(I) and silver(I) N-heterocyclic carbene complexes.Malaria journal · 2026Article
- Effect of Stereochemistry on the Antiplasmodial Activity and Metabolomic Profile of Novel Tadalafil Analogues.ACS medicinal chemistry letters · 2026Article
- Advances in Natural Product Extraction: Established and Emerging Technologies.Molecules (Basel, Switzerland) · 2026Review
- Turn-on quinoline probe for selective sensing of hypochlorite in live cells.Scientific reports · 2026Article
- From Forestry By-Product to Functional Food Ingredient Innovation: Antiproliferative, Antimetastatic and Antiplasmodial Activities of Norway Spruce Sawdust Extract.Foods (Basel, Switzerland) · 2026Article
- Antimalarial Activity and Safety Profile of Gaysorn-Tang-Ha (GSTH): A Thai Herbal Recipe Evaluated in an ICR Model.Scientifica · 2026Article
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Aqueous extract of Enantia chlorantha Oliv. demonstrates antimalarial activity and improves redox imbalance and biochemical alterations in mice.BMC complementary medicine and therapies · 2025Article
- Evaluation of In Vitro Inhibition ofMicroorganisms · 2024Article
- Synthesis,Antidiabetic and Antitubercular Evaluation of Quinoline-pyrazolopyrimidine hybrids and Quinoline-4-Arylamines.ChemistryOpen · 2024Article
- Reaction Pattern and Mechanistic Aspects of Iodine and Iodine-Based Reagents in Selenylation of Aliphatic, Aromatic, and (Hetero)Cyclic Systems.Topics in current chemistry (Cham) · 2024Review
- Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.Toxicology letters · 2024Article
- The Malaria Burden: A South African Perspective.Journal of tropical medicine · 2024Review
- Roles of Virtual Screening and Molecular Dynamics Simulations in Discovering and Understanding Antimalarial Drugs.International journal of molecular sciences · 2023Review
- Identifying inhibitors of β-haematin formation with activity against chloroquine-resistant Plasmodium falciparum malaria parasites via virtual screening approaches.Scientific reports · 2023Article
- Potential Benefits of Lycopene Consumption: Rationale for Using It as an Adjuvant Treatment for Malaria Patients and in Several Diseases.Nutrients · 2022Review
- The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures.BMC biology · 2022Article
- Multimodal Investigation into the Interaction of Quinacrine with Microcavity-Supported Lipid Bilayers.Langmuir : the ACS journal of surfaces and colloids · 2022Article
- Insights into the Mechanisms ofAntioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malaria caused by Plasmodium affects millions people worldwide. Plasmodium consumes hemoglobin during its intraerythrocytic stage leaving toxic heme. Parasite detoxifies free heme through formation of hemozoin (β-hematin) pigment. Proteolysis of hemoglobin and formation of hemozoin are two main targets for antimalarial drugs. Quinoline antimarial drugs and analogs (β-carbolines or nitroindazoles) were studied as inhibitors of β-hematin formation. The most potent inhibitors were quinacrine, chloroquine, and amodiaquine followed by quinidine, mefloquine and quinine whereas 8-hydroxyquinoline and β-carbolines had no effect. Compounds that inhibited β-hematin increased free hemin that promoted peroxidative reactions as determined with TMB and ABTS substrates. Hemin-catalyzed peroxidative reactions were potentiated in presence of proteins (i.e. globin or BSA) while antioxidants and peroxidase inhibitors decreased peroxidation. Free hemin increased by chloroquine action promoted oxidative reactions resulting in inhibition of proteolysis by three cysteine proteases: papain, ficin and cathepsin B. Glutathione reversed inhibition of proteolysis. These results show that active quinolines inhibit hemozoin and increase free hemin which in presence of H
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