Publication:
Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparum

Issued Date

2003-01-17

Resource Type

Article

ISSN

09680896

DOI

10.1016/S0968-0896(02)00344-9

Other identifier(s)

2-s2.0-0037449359

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Bioorganic and Medicinal Chemistry. Vol.11, No.2 (2003), 217-224

Suggested Citation

Tirayut Vilaivan, Neungruthai Saesaengseerung, Deanpen Jarprung, Sumalee Kamchonwongpaisan, Worachart Sirawaraporn, Yongyuth Yuthavong Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparum. Bioorganic and Medicinal Chemistry. Vol.11, No.2 (2003), 217-224. doi:10.1016/S0968-0896(02)00344-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/20773

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Title

Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V+S108T mutant dihydrofolate reductase of Plasmodium falciparum

Author(s)

Tirayut Vilaivan
 Neungruthai Saesaengseerung
 Deanpen Jarprung
 Sumalee Kamchonwongpaisan
 Worachart Sirawaraporn
 Yongyuth Yuthavong

Other Contributor(s)

Chulalongkorn University
 Thailand National Center for Genetic Engineering and Biotechnology
 Mahidol University

Abstract

An efficient method to synthesize solution-phase combinatorial library of 1-aryl-4,6-diamino-1,2-dihydro-1,3,5-triazine was developed. The strategy involved an acid-catalyzed cyclocondensation between arylbiguanide hydrochlorides and carbonyl compounds in the presence of triethyl orthoacetate as water scavenger. A 96-membered combinatorial library was constructed from 6 aryl biguanides and 16 carbonyl compounds. Screening of the library by iterative deconvolution method revealed two candidate leads which are equally active against wild-type Plasmodium falciparum dihydrofolate reductase, but are about 100-fold more effective against the A16V+S108T mutant enzyme as compared to cycloguanil. © 2002 Elsevier Science Ltd. All rights reserved.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Chemistry
 Pharmacology, Toxicology and Pharmaceutics

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/20773

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Scopus 2001-2005