3D-QSAR and molecular docking studies of 1,3,5-triazene-2,4-diamine derivatives against r-RNA: Novel bacterial translation inhibitors

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• 作者：Y. Nataraja Sekhar ; M. Ravi Shashi Nayana ; N. Sivakumari ; Muttineni Ravikumar ; S.K. Mahmood
• 关键词：QSAR ; CoMFA ; CoMSIA ; Docking ; Antibiotics ; Translation inhibitors ; 1 ; 3 ; 5-Triazine-2 ; 4-diamine derivatives ; r-RNA
• 刊名：Journal of Molecular Graphics and Modelling
• 出版年：2008
• 期刊代码：77_10933263
• 类别：cp
• 出版时间：June 2008
• 卷：26
• 期：8
• 页码：1338-1352
• 文件大小：1828 K

摘要

Aminoglycoside mimetics inhibit bacterial translation by interfering with the ribosomal decoding site. To elucidate the structural properties of these compounds important for antibacterial activity, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to a set of 56 aminoglycosides mimetics. The successful CoMFA model yielded the leave-one-out (LOO) cross-validated correlation coefficient (q²) of 0.708 and a non-cross-validated correlation coefficient (r²) of 0.967. CoMSIA model gave q² = 0.556 and r² = 0.935. The CoMFA and CoMSIA models were validated with 36 test set compounds and showed a good d=retrieve&_udi=B6TGP-4RTM357-1&_mathId=mml9&_user=1067359&_cdi=5260&_rdoc=18&_acct=C000050221&_version=1&_userid=10&md5=bfc63bc5f3ed4fd5bf5d3364c227b208">direct.com/cache/MiamiImageURL/B6TGP-4RTM357-1-29/0?wchp=dGLbVlb-zSkWz" alt="View the MathML source" title="View the MathML source" align="absbottom" border="0" height=21 width="28"/> of 0.624 and 0.640, respectively. Contour maps of the two QSAR approaches show that electronic effects dominantly determine the binding affinities. These obtained results were agreed well with the experimental observations and docking studies. The results not only lead to a better understanding of structural requirements of bacterial translation inhibitors but also can help in the design of novel bacterial translation inhibitors.