ABSTRACT: 4-N-carbamic
acid-4’-dimetylpipodopylotoxin and its derivatives are compounds which are
synthesized from etoposide (VP 16). These compounds are used as anticancer
medicine because they inhibit DNA topoisomerase II enzyme. The enzyme
participates in controlling breaking process of DNA double helix bounding in
cancer cell. It makes cancer growing cease and dies because cell can not
replicate. However, the compound insoluble in water, make a medicine resistant,
inhibit metabolism system and poison. It needs to design a modification of new
compounds from carbamic acid derivatives which have higher activity. Structure
modification was done using Quantitative Structure Activity Relationship (QSAR)
which was a computational chemistry application in medicine design process.
This research used semiempiris AM1 method to determine the best QSAR equation
based on multilinear regression analysize, with log 1/IC50 as dependent
variable and independent variables were atomic net charge of qN29, qC30, qO31,
qO32, dipole moment, n-octanol-water coefficient partition (Log P), and
polarity. The best QSAR equation in this research was : Log 1/IC50 = 4.871 +
12.738 qN29 + 33.183 qC30 + 28.015 qO31 – 3.6 x 10-2 polarity, with N = 13, r
=0.907, SE = 0.13025, Fcount/Ftable = 1.901, PRESS = 0.1357. Based on the best
QSAR equation, the prediction compounds were 1, 2, 3, 8, and 22 with each IC50
theoretical value were 0.032, 0.034, 0.036, and 0.098 µM.
Keywords: carbamic acid, QSAR,
semiempiris AM1
Penulis: Senny Widyaningsih,
Purwati, Riyadi
Kode Jurnal: jpkimiadd070017
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