A quantitative structure-activity relationship study on serotonin 5-HT6 receptor ligands: indolyl and piperidinyl sulphonamides

• Published in: SAR and QSAR in environmental research Vol. 21; no. 3-4; pp. 369 - 388
• Main Authors: Sharma, B.K., Singh, P., Sarbhai, K., Prabhakar, Y.S.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01-04-2010
• Subjects: combinatorial protocol in multiple linear regression (CP-MLR); DRAGON descriptors; Humans; Indoles - chemistry; Indoles - metabolism; indolyl and piperidinyl sulphonamides; Models, Statistical; partial least squares (PLS) analysis; Protein Binding; Quantitative Structure-Activity Relationship; receptor; Receptors, Serotonin - metabolism; serotonin 5-HT; Sulfonamides - chemistry; Sulfonamides - metabolism
• ISSN: 1062-936X; 1029-046X
• DOI: 10.1080/10629361003773997

The serotonin 5-HT
6
binding affinity of indolyl- and piperidinyl-sulphonamide derivatives has been analysed with topological and molecular features with DRAGON software. Analysis of the structural features in conjunction with the biological endpoints in combinatorial protocol in multiple linear regression (CP-MLR) led to the identification of 25 descriptors for modelling the activity. The study clearly suggested the role of an average Randic-type eigenvector-based index from adjacency matrix, VRA2, number of secondary aliphatic amines, nNHR, the sum of the topological distance between N and O, T(N···O), ring tertiary carbon atoms, nCrHR, and CH2RX type fragment, C-006, in a molecular structure to optimize the 5-HT
6
binding affinities of titled compounds. The PLS analysis confirmed the dominance of information content of CP-MLR identified descriptors for modelling the activity when compared with those of leftover ones.