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Structural and Functional Diversities of the Hexadecahydro-1H-cyclopenta[a]phenanthrene Framework, a Ubiquitous Scaffold in Steroidal Hormones.
Choudhury, Chinmayee; Deva Priyakumar, U; Narahari Sastry, G.
Afiliação
  • Choudhury C; Centre for Molecular Modeling, Indian Institute of Chemical Technology, Hyderabad, INDIA.
  • Deva Priyakumar U; Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information and Technology, Hyderabad, INDIA.
  • Narahari Sastry G; Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information and Technology, Hyderabad, INDIA. deva@iiit.ac.in.
Mol Inform ; 35(3-4): 145-57, 2016 04.
Article em En | MEDLINE | ID: mdl-27491924
Hexadecahydro-1H-cyclopenta[a]phenanthrene framework (HHCPF) has been considered as one of the privileged scaffolds due to its versatile presence in many biologically essential molecules. In our quest to unravel the privileged nature of this framework, we undertook a systematic analysis of target binding and Absorption, Distribution, Metabolism, Elimination, Toxicity (ADMET)/physicochemical properties of 110 drugs containing HHCPF reported in DrugBank. Effect of number and positions of double bonds in the framework and substitutions at each carbon position on the target selectivity as well as drug like properties of these drugs were studied. Fifteen different scaffolds based on the numbers and positions of double bonds in the HHCPF were identified among these drugs. The optimum number of double bonds present in the HHCPF scaffolds was observed to be one to three, and one particular positional isomer is predominant among many scaffolds with same numbers of double bonds. Docking studies reveal the role of substituents at different positions to make specific interactions with their respective targets. Based on the docking interactions, we proposed structure based e-Pharmacophore models for seven important targets of HHCPF drugs. Good correlations were observed between the substitutions carbon positions 3 and 17 of the scaffolds and ADMET properties of the HHCPF drugs. This work enables preliminary prediction of the target selectivity and ADMET properties of a new HHCPF molecule based on the scaffold, substituents and the pharmacophoric features.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenantrenos / Esteroides Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenantrenos / Esteroides Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article