261000-67-3Relevant academic research and scientific papers
Parallel inhibition of amino acid efflux and growth of erythrocytic Plasmodium falciparum by mefloquine and non-piperidine analogs: Implication for the mechanism of antimalarial action
Ghavami, Maryam,Dapper, Christie H.,Dalal, Seema,Holzschneider, Kristina,Klemba, Michael,Carlier, Paul R.
supporting information, p. 4846 - 4850 (2016/09/13)
Despite the troubling psychiatric side-effects it causes in some patients, mefloquine (MQ) has been used for malaria prophylaxis and therapy, due to its activity against all Plasmodium species, its ease of dosing, and its relative safety in children and pregnant women. Yet at present there is no consensus on the mechanism of antimalarial action of MQ. Two leading hypotheses for the mechanism of MQ are inhibition of heme crystallization and inhibition of host cell hemoglobin endocytosis. In this report we show that MQ is a potent and rapid inhibitor of amino acid efflux from intact parasitized erythrocytes, which is a measure of the in vivo rate of host hemoglobin endocytosis and catabolism. To further explore the mechanism of action of MQ, we have compared the effects of MQ and 18 non-piperidine analogs on amino acid efflux and parasite growth. Among these closely related compounds, an excellent correlation over nearly 4 log units is seen for 50% inhibition concentration (IC50) values for parasite growth and leucine efflux. These data and other observations are consistent with the hypothesis that the antimalarial action of these compounds derives from inhibition of hemoglobin endocytosis.
Structure-activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum
Milner, Erin,McCalmont, William,Bhonsle, Jayendra,Caridha, Diana,Carroll, Dustin,Gardner, Sean,Gerena, Lucia,Gettayacamin, Montip,Lanteri, Charlotte,Luong, ThuLan,Melendez, Victor,Moon, Jay,Roncal, Norma,Sousa, Jason,Tungtaeng, Anchalee,Wipf, Peter,Dow, Geoffrey
supporting information; experimental part, p. 1347 - 1351 (2010/07/02)
Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure-activity relationship for this library of quinoline methanols.
4-quinolinemethanol derivatives as purine receptor antagonists (II)
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, (2008/06/13)
Use of a compound of formula (I) as defined herein, or a pharmaceutically acceptable salt or prodrug thereof, in the manufacture of a medicament for the treatment or prevention of a disorder in which the blocking of purine receptors, particularly adenosin
