Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase

Shafinaz F. Chowdhury; Ramon  Hurtado Guerrero; Reto Brun; Luis M.  Ruiz-Perez; Dolores  Gonzalez Pacanowska; Ian H. Gilbert

doi:10.1080/1475636021000059083

Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase

Shafinaz F. Chowdhury, Ramon Hurtado Guerrero, Reto Brun, Luis M. Ruiz-Perez, Dolores Gonzalez Pacanowska, Ian H. Gilbert

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

Dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. Work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. Modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Various compounds were prepared and evaluated against both the recombinant enzymes and the intact organisms. The presence of a substituent had a small or negative effect on activity against the enzyme or intact parasites compared to unsubstituted compounds.

Original language	English
Pages (from-to)	293-302
Number of pages	10
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	17
Issue number	5
DOIs	https://doi.org/10.1080/1475636021000059083
Publication status	Published - 2002

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Chowdhury, S. F., Hurtado Guerrero, R., Brun, R., Ruiz-Perez, L. M., Gonzalez Pacanowska, D., & Gilbert, I. H. (2002). Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Journal of Enzyme Inhibition and Medicinal Chemistry, 17(5), 293-302. https://doi.org/10.1080/1475636021000059083

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title = "Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase",

abstract = "Dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. Work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. Modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Various compounds were prepared and evaluated against both the recombinant enzymes and the intact organisms. The presence of a substituent had a small or negative effect on activity against the enzyme or intact parasites compared to unsubstituted compounds.",

author = "Chowdhury, {Shafinaz F.} and {Hurtado Guerrero}, Ramon and Reto Brun and Ruiz-Perez, {Luis M.} and {Gonzalez Pacanowska}, Dolores and Gilbert, {Ian H.}",

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Chowdhury, SF, Hurtado Guerrero, R, Brun, R, Ruiz-Perez, LM, Gonzalez Pacanowska, D & Gilbert, IH 2002, 'Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 17, no. 5, pp. 293-302. https://doi.org/10.1080/1475636021000059083

TY - JOUR

T1 - Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase

AU - Chowdhury, Shafinaz F.

AU - Hurtado Guerrero, Ramon

AU - Brun, Reto

AU - Ruiz-Perez, Luis M.

AU - Gonzalez Pacanowska, Dolores

AU - Gilbert, Ian H.

PY - 2002

Y1 - 2002

N2 - Dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. Work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. Modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Various compounds were prepared and evaluated against both the recombinant enzymes and the intact organisms. The presence of a substituent had a small or negative effect on activity against the enzyme or intact parasites compared to unsubstituted compounds.

AB - Dihydrofolate reductase is a drug target that has not been thoroughly investigated in leishmania and trypanosomes. Work has previously shown that 5-benzyl-2,4-diaminopyrimidines are selective inhibitors of the leishmanial and trypanosome enzymes. Modelling predicted that alkyl/aryl substitution on the 6-position of the pyrimidine ring should increase enzyme activity of 5-benzyl-2,4-diaminopyrimidines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Various compounds were prepared and evaluated against both the recombinant enzymes and the intact organisms. The presence of a substituent had a small or negative effect on activity against the enzyme or intact parasites compared to unsubstituted compounds.

U2 - 10.1080/1475636021000059083

DO - 10.1080/1475636021000059083

M3 - Article

SN - 1475-6366

VL - 17

SP - 293

EP - 302

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

IS - 5

ER -

Synthesis and testing of 5-benzyl-2,4-diaminopyrimidines as potential inhibitors of leishmanial and trypanosomal dihydrofolate reductase

Abstract

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