Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H16O6.2C11H14ClN5 |
| Molecular Weight | 891.8 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1(C)N=C(N)N=C(N)N1C2=CC=C(Cl)C=C2.CC3(C)N=C(N)N=C(N)N3C4=CC=C(Cl)C=C4.OC(=O)C5=CC6=C(C=CC=C6)C(CC7=C8C=CC=CC8=CC(C(O)=O)=C7O)=C5O
InChI
InChIKey=LUNRMKZYOGNOTR-UHFFFAOYSA-N
InChI=1S/C23H16O6.2C11H14ClN5/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;2*1-11(2)16-9(13)15-10(14)17(11)8-5-3-7(12)4-6-8/h1-10,24-25H,11H2,(H,26,27)(H,28,29);2*3-6H,1-2H3,(H4,13,14,15,16)
Cycloguanil is a dihydrofolate reductase inhibitor and is a metabolite of the antimalarial drug proguanil. The parent drug proguanil was suggested to contribute to the antimalarial activity as well, but the mechanism of action is unknown. Proguanil is a prodrug that is metabolized to its main active metabolite, cycloguanil, mostly via CYP2C19. There is significant variation in proguanil pharmacokinetics.12 CYP2C19 is the predominant enzyme catalyzing the bioactivation of proguanil to cycloguanil. Cycloguanil is one of the few antimalarial drugs that act on both the erythrocytic and on the pre-erythrocytic (hepatic) forms of the malaria parasites. Although cycloguanil is not currently in general use as an antimalarial, the continuing development of resistance to current antimalarial drugs has led to renewed interest in studying the use of cycloguanil in combination with other drugs.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Malaria: use of restriction endonuclease digestion and mutation-specific PCR for antifolate resistance isolate detection. | 2003 Mar |
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| Pharmacodynamic interactions among atovaquone, proguanil and cycloguanil against Plasmodium falciparum in vitro. | 2003 May-Jun |
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| The chemotherapy of rodent malaria. LXII. Drug combinations to impede the selection of drug resistance, part 5: rates of development of resistance to some inhibitors of folate metabolism and to artesunate. | 2004 Dec |
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| Translational up-regulation of antifolate drug targets in the human malaria parasite Plasmodium falciparum upon challenge with inhibitors. | 2004 Jul |
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| Homology building as a means to define antigenic epitopes on dihydrofolate reductase (DHFR) from Plasmodium falciparum. | 2004 Jun 12 |
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| In vitro metabolism of phenoxypropoxybiguanide analogues in human liver microsomes to potent antimalarial dihydrotriazines. | 2005 Apr 21 |
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| Malaria epidemic and drug resistance, Djibouti. | 2005 Feb |
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| Syntheses of 2,4,6-trisubstituted triazines as antimalarial agents. | 2005 Feb 1 |
|
| Novel alleles of Plasmodium falciparum dhfr that confer resistance to chlorcycloguanil. | 2005 Jan |
|
| In vitro recrudescence of Plasmodium falciparum parasites suppressed to dormant state by atovaquone alone and in combination with proguanil. | 2005 Jan |
|
| The chemotherapy of rodent malaria. LXIII. Drug combinations to impede the selection of drug resistance, part 6: the potential value of chlorproguanil and dapsone in combination, and with the addition of artesunate. | 2005 Jul |
|
| Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni. | 2005 Jul |
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| Malarial (Plasmodium falciparum) dihydrofolate reductase-thymidylate synthase: structural basis for antifolate resistance and development of effective inhibitors. | 2005 Mar |
|
| Stoichiometric selection of tight-binding inhibitors by wild-type and mutant forms of malarial (Plasmodium falciparum) dihydrofolate reductase. | 2005 Mar 1 |
|
| Plasmodium falciparum: interaction of shikimate analogues with antimalarial drugs. | 2005 Nov |
|
| [Chemosusceptibility analysis of Plasmodium falciparum imported from Comoros to Marseilles, France in 2001-2003]. | 2005 Oct |
|
| A simple dual selection for functionally active mutants of Plasmodium falciparum dihydrofolate reductase with improved solubility. | 2005 Oct |
|
| The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third-trimester pregnant women. | 2005 Sep |
|
| Sensitive method for the quantitative determination of proguanil and its metabolites in rat blood and plasma by liquid chromatography-mass spectrometry. | 2006 Jan 18 |
|
| Effect of honey on CYP3A4, CYP2D6 and CYP2C19 enzyme activity in healthy human volunteers. | 2007 Apr |
|
| A novel Plasmodium falciparum expression system for assessing antifolate resistance caused by mutant P. vivax dihydrofolate reductase-thymidylate synthase. | 2007 Aug 1 |
|
| Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed? | 2007 Feb 16 |
|
| Simultaneous determination of monodesethylchloroquine, chloroquine, cycloguanil and proguanil on dried blood spots by reverse-phase liquid chromatography. | 2007 Feb 19 |
|
| Rapid dissemination of Plasmodium falciparum drug resistance despite strictly controlled antimalarial use. | 2007 Jan 3 |
|
| The role of tryptophan-48 in catalysis and binding of inhibitors of Plasmodium falciparum dihydrofolate reductase. | 2007 Jun |
|
| Analysis of sulphadoxine/pyrimethamine resistance-conferring mutations of Plasmodium falciparum from Mozambique reveals the absence of the dihydrofolate reductase 164L mutant. | 2007 Mar 23 |
|
| Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran. | 2007 Nov 13 |
|
| Antimalarial drug susceptibility and point mutations associated with drug resistance in 248 Plasmodium falciparum isolates imported from Comoros to Marseille, France in 2004 2006. | 2007 Sep |
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| Modelling and informatics in the analysis of P. falciparum DHFR enzyme inhibitors. | 2008 |
|
| The usefulness of twenty-four molecular markers in predicting treatment outcome with combination therapy of amodiaquine plus sulphadoxine-pyrimethamine against falciparum malaria in Papua New Guinea. | 2008 Apr 19 |
|
| Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents. | 2008 Dec 15 |
|
| Plasmodium falciparum malaria and atovaquone-proguanil treatment failure. | 2008 Feb |
|
| Role of specific cytochrome P450 isoforms in the conversion of phenoxypropoxybiguanide analogs in human liver microsomes to potent antimalarial dihydrotriazines. | 2008 Feb |
|
| Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy. | 2008 Feb 12 |
|
| Molecular epidemiology of drug-resistant malaria in western Kenya highlands. | 2008 Jul 31 |
|
| Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo. | 2008 Mar 5 |
|
| Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer. | 2008 May |
|
| Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia. | 2008 May 21 |
|
| Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola. | 2008 Nov 17 |
|
| Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil. | 2008 Nov 20 |
|
| A novel in silico approach to drug discovery via computational intelligence. | 2009 Apr |
|
| Interactions between cycloguanil derivatives and wild type and resistance-associated mutant Plasmodium falciparum dihydrofolate reductases. | 2009 Apr |
|
| Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria. | 2009 Apr 14 |
|
| Analysis of genetic mutations associated with anti-malarial drug resistance in Plasmodium falciparum from the Democratic Republic of East Timor. | 2009 Apr 9 |
|
| Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa. | 2009 Feb |
|
| Molecular characterization of antifolates resistance-associated genes, (dhfr and dhps) in Plasmodium vivax isolates from the Middle East. | 2009 Jan 28 |
|
| Structure-activity relationship and comparative docking studies for cycloguanil analogs as PfDHFR-TS inhibitors. | 2009 Jul |
|
| WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures. | 2009 May 1 |
|
| A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. | 2009 May 4 |
|
| Catalytic and ligand-binding characteristics of Plasmodium falciparum serine hydroxymethyltransferase. | 2009 Nov |
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WHO-ATC |
P01BB02
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CHEMBL747
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609-78-9
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77830
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1527
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443381
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TCO0SY4N3D
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m3984
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100000083732
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DTXSID40209737
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C171767
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
