2002
DOI: 10.1021/jm0108707
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Novel Short Chain Chloroquine Analogues Retain Activity Against Chloroquine Resistant K1 Plasmodium falciparum

Abstract: A series of short chain chloroquine (CQ) derivatives have been synthesized in one step from readily available starting materials. The diethylamine function of CQ is replaced by shorter alkylamine groups (4-9) containing secondary or tertiary terminal nitrogens. Some of these derivatives are significantly more potent than CQ against a CQ resistant strain of Plasmodium falciparum in vitro. We conclude that the ability to accumulate at higher concentrations within the food vacuole of the parasite is an important … Show more

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Cited by 127 publications
(122 citation statements)
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“…The alkylamine sidechains allow for structural modification of the 4-aminoquinolines, resulting in compounds that have different lipophilicity and drug-resistance profiles (Kouznetsov & Gómez-Barrio 2009). Substitutions on the distal amino sidechain of CQ derivatives increase the activity and decrease the cross-resistance to CQ (Stocks et al 2002).…”
Section: Drug Combinations and Hybrids Used In Antimalarial Chemothermentioning
confidence: 99%
“…The alkylamine sidechains allow for structural modification of the 4-aminoquinolines, resulting in compounds that have different lipophilicity and drug-resistance profiles (Kouznetsov & Gómez-Barrio 2009). Substitutions on the distal amino sidechain of CQ derivatives increase the activity and decrease the cross-resistance to CQ (Stocks et al 2002).…”
Section: Drug Combinations and Hybrids Used In Antimalarial Chemothermentioning
confidence: 99%
“…The return of tuberculosis was declared by World Health Organization (WHO) as a global emergency compared to a hypothetic third world war with 9 million new TB cases and two million deaths reported each year 2,3 ; about one-third of the world's population is already infected with M. tuberculosis 4 . The quinoline was reported to exhibit various biological activity such as antiviral 5,6 , antiamoebic 7 , anti-inflammatory 8,9 as well as antimalarial 10,11 activity. In addition, the discovery of nalidixic acid, a urinary tract antimicrobial drug 12 , prompted the synthesis of many quinoline derivatives and evaluationfor their antimicrobial activity [13][14][15] and antibacterial activity.…”
Section: Tuberculosis (Tb) Is a Global Epidemic Caused By Various Strmentioning
confidence: 99%
“…In our efforts to develop effective antimalarial agents, earlier we have reported design, synthesis and antimalarial activity of several side chain-modified 4-aminoquinolines [13][14][15][16] . We have demonstrated that 4-aminoquinoline-derived guanidine and tetramethylguanidine analogues ( Figure 1A) with altered chain length exhibit promising activity against CQ-sensitive 7 . Earlier we have also demonstrated that modification on 4-aminoquinoline lateral side chain with thiazolidine-4-one ring substitution ( Figure 1B) has led to compounds with improved antimalarial activity, and some of these compounds were indeed more effective than CQ 14 .…”
Section: Introductionmentioning
confidence: 98%
“…Based on this affirmation, a number of groups have developed short chain analogues of 4-aminoquinoline derivatives, which are significantly more potent than CQ against a CQ-resistant strain of Plasmodium falciparum in in vitro studies 6,7 . CQ and closely related 4-aminoquinolines form a complex with (Fe(III)FPIX) haematin, which is generated in the digestive vacuole of the intraerythrocytic malaria parasite as a result of proteolysis of host haemoglobin [7][8][9] . Free haematin is cytotoxic for malaria parasite and it is sequestered in the form of haemozoin.…”
Section: Introductionmentioning
confidence: 99%