3D-QSAR study on heterocyclic topoisomerase II inhibitors using CoMSIA

SAR and QSAR in Environmental Research
Betul Tekiner-GulbasI Yalcin

Abstract

Selective topoisomerase II (Topo II) inhibitors have interested to a great extent for the design of new antitumoral compounds in recent years. Comparative molecular similarity indices analysis (CoMSIA) was performed on a series of previously synthesized benzoxazole, benzimidazole, and oxazolo(4,5-b)pyridine derivatives as eukaryotic Topo II inhibitors. A training set of 16 heterocyclic compounds was used to establish the CoMSIA model. They were constructed and geometrically optimized using SYBYL v7.0. The predictive ability of the model was assessed using a test set of 7 compounds. The best model has demonstrated a good fit having r2 value of 0.968 and cross-validated coefficient q2 value as 0.562 including steric and hydrophobic fields. The hydrophobic interactions showed a dominant role for increasing Topo II inhibitor activity and hydrophilic substituent was found more important than hydrophobic one on the 5 or 6 position of benzazole moiety. The model obtained from the present study can be useful for the modification and/or evaluation of the development of new Topo II inhibitors as potential antitumor compounds.

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Citations

May 22, 2007·SAR and QSAR in Environmental Research·B Tekiner-GulbasI Yalcin
Sep 2, 2011·Chemical & Pharmaceutical Bulletin·Hadi AdibiDavood Nematollahi
Feb 27, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·O UnsalanI Yalcin
Apr 3, 2012·Chemical & Pharmaceutical Bulletin·Venkatapuram PadmavathiAdivireddy Padmaja
Mar 18, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Emine OksuzogluIsmail Yalcin
Dec 12, 2012·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·J B BhagyasreeEsin Aki
Jun 6, 2008·European Journal of Medicinal Chemistry·Tugba ErtanEsin Aki
Jul 9, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·J B BhagyasreeOzlem Temiz-Arpaci
Dec 21, 2016·ACS Medicinal Chemistry Letters·Garima PriyadarshaniUttam C Banerjee

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