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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. March 2003, Volume 2, Number 3, 128-136 |
QSAR Study on Some Dihydrofolate Reductase Inhibitors
Bikash Debnath, Satya Prakash Vishnoi, Biswanath Sa, and Tarun Jha
Internet Electron. J. Mol. Des. 2003, 2, 128-136
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Abstract:
Dihydrofolate reductase (DHFR) inhibitors have proved to
be of value as antibacterial, antimalarial, and antitumor
agents. Some 2,4-diamino-5-methyl-6-[(substituted
anilino)methyl]pyrrido[2,3-d]pyrimidines were reported
earlier as DHFR inhibitors. Using non-parabolic Hansch
models, a QSAR study was performed in an attempt to find
out the required physicochemical and structural features of
these compounds for DHFR inhibition. This study revealed
the importance of resonance effect at R2 and R3 positions
and sum of molar refractivity (ΣMR) at R2, R3, R4, and R5
positions of the ring C. Lipophilicity of the whole molecule
(log P) also played an important role. The presence of
OCH3 group at R4 of the phenyl C ring and CH3 at R1 of
anilino N might be advantageous to DHFR inhibition. This
QSAR study is beneficial for future studies to carry out
further tailoring of this type of compounds with an
objective to increase DHFR inhibitory activity.
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