In Silico-Based Structural Analysis of Arylthiophene Derivatives for FTase Inhibitory Activity, hERG, and Other Toxic Effects

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Hari S H N Narayana Moorthy (Author) Other; Sergio F Sousa (Author) FCUP; Maria J Ramos (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Journal of Biomolecular Screening

Vol. 16

Pages: 1037-1046

ISSN: 1087-0571

Publisher: SAGE Publications

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 19 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-002-M3S

DOI: 10.1177/1087057111414899

Abstract (EN): In the present investigation, the authors have performed an in silico-based analysis on a series of arylthiophene derivatives for the determination of their structural features responsible for farnesyltransferase (FTase) inhibitory activity, hERG blocking activity, and toxicity by quantitative structure-activity relationship and pharmacophore analysis techniques. The statistically significant models derived through multiple linear regression analysis were validated by different validation methods. The applicability of the descriptors contributed in the selected models show that the polar and polarizable properties on the van der Waals (vdW) surface area of the molecules are important for the FTase inhibitory and hERG blocking activities, while being detrimental for the toxicity of the molecules. It is interesting to note that the topological properties, molecular flexibility, and connectivity of the molecules are positively correlated to all the activities (FTase inhibition, hERG blocking, and toxicity). This implies that the flexibility of the molecules is the common feature for interaction in all targets, whereas the presence of polar groups on the molecular surface (vdW) is a determinant for the favorable (FTase inhibition) or unwanted effect (hERG blocking and toxicity) of the molecules. The pharmacophore analysis of the molecules demonstrated that the aromatic/hydrophobicity and polarizability features are important pharmacophore contours favorable for these activities. (Journal of Biomolecular Screening 2011;16:1037-1046)

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10