QSAR Studies of New Pyrido[3,4-b ]indole Derivatives as Inhibitors of Colon and Pancreatic Cancer Cell Proliferation

Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents
Hemantkumar DeokarJohn K Buolamwini

Abstract

We have discovered a new class of pyrido[b]bindole derivatives that show potent and broad spectrum anticancer activity with IC50 values down to submicromolar levels. Structure-activity relationship data acquired with the compounds as antiproliferative agents against several cancer cell lines, i.e. human HCT116 colon cancer cell line, and HPAC, Mia-PaCa2 and Panc-1 pancreatic cancer cell lines, were subjected to two different QSAR modeling methods. A kernel-based partial least squares (KPLS) regression analysis with chemical 2D fingerprint descriptors, and a PHASE pharmacophore alignment with 3D-QSAR study. The KPLS method afforded successful predictive QSAR models for antiproliferative activity of the HCT116 colon cell line and on two of the pancreatic cancer cell lines HPAC and Mia-PaCa2, with the following statistics: R2s of 0.99, 0.99 and 0.98, for training set coefficients of determination, and external test set predictive r2s of 0.70, 0.58 and 0.70, respectively. The best 2D fingerprint descriptor for both the HCT116 and HPAC data out of the eight finger prints utilized was the atom triplet fingerprint; whereas the one that worked best for the Mia-PaCa2 data was the linear fingerprint descriptor. The PHASE pharmacophore ba...Continue Reading

References

Sep 19, 2003·Journal of Computer-aided Molecular Design·Alexander GolbraikhAlexander Tropsha
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Aug 2, 2013·Journal of Chemical Information and Modeling·Yuling AnSteven L Dixon

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Citations

Oct 7, 2019·Medicinal Research Reviews·Wei WangRuiwen Zhang

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Software Mentioned

PHASE
LigPrep
PHASE ( Pharmacophore Alignment and Scoring Engine )
Maestro Suite
Canvas
MOLPRINT2D
Schrodinger
Linux

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