In silico based structural analysis of some piperidine analogs as farnesyltransferase inhibitors

• Published in: Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 8; no. 5; p. 853
• Main Authors: Moorthy, Narayana Subbiah Hari Narayana, Sousa, Sergio F, Ramos, Maria J, Fernandes, Pedro A
• Format: Journal Article
• Language: English
• Published: Netherlands 01-09-2012
• Subjects: Computer Simulation; Enzyme Inhibitors - chemistry; Farnesyltranstransferase - antagonists & inhibitors; Farnesyltranstransferase - chemistry; Humans; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Molecular Structure; Piperidines - chemistry; Quantitative Structure-Activity Relationship; Research Design; Solubility; Static Electricity; Thermodynamics
• ISSN: 1875-6638
• DOI: 10.2174/157340612802084171

In silico based QSAR and pharmacophore analyses of a series of piperidine derivatives were performed in order to investigate the structural features of the derivatives responsible for FTase inhibitory activity. The results derived from the QSAR analysis show that the FTase inhibitory activity mediated by the vdW surface area features such as partial charge (PEOE_VSA and Q_VSA) and v_surf (hydrophobic integy moment) of the molecules. The positive contribution of the partial charge descriptors such as Q_VSA_FPNEG and PEOE_VSA-4 reveal that the fractional negative charge on the vdW surface of the molecules and the aqueous solubility (LogS) of the molecules are important for the FTase inhibitory activity. While the hydrophobic integy moment reveals that a clear separation between the hydrophobic and the hydrophilic region in the molecules is important with electrostatic groups (fractional negative charge) for better activity. The pharmacophore analyses of the piperidine derivatives also show that the aromatic, acceptor and donor groups on the molecule favorable for the FTase inhibitory activity.