CP-MLR Directed QSAR Rationales for the 1-aryl Sulfonyl Tryptamines as 5-HT6 Receptor Ligands

Abstract

A QSAR study has been carried out to rationalize the 5-HT 6 receptor binding affinities of the 1-aryl sulfonyl tryptamine derivatives using Dragon descriptors. A higher value of molecular symmetry and topology accounting Randic shape index descriptor PW4 (path/walk 4) would be favorable to improve the binding affinity. Presence of more number of bromine atoms (descriptor nBR) and presence of such structural fragment in which a hydrogen atom attached to sp3 hybridized carbon with no hetero atom rather than one hetero atom attached to next carbon atom (descriptors H-046 and H-052) will be supportive to the activity. The prevalence of atomic properties to explain the binding affinity is evident from the associations of polarizability to the path length 7 of Moran autocorrelation (MATS7p), masses to eigenvalues n.2 and 7 of Burden m atrix (BELm2 and BEHm7), Sanderson electronegativity to highest eigenvalue n.2 Burden matrix (BEHe2) and van der Waals volume to path length 8 of Geary autocorrelation (GATS8v) and charge content in terms of topological and mean topological charge indices (GGI3 and JGI2). The dominance of the information content of the descriptors, emerged in CP-MLR models, has also confirmed by the PLS analysis. Original Research Article Choudhary et al.; BJPR, 8(3): 1-17, 2015; Article no.BJPR.18732 2 The derived QSAR models and descriptors shared in these models revealed that the substituents of tryptamine moiety have sufficient scope for further modification. Keywords: QSAR; 1-aryl sulfonyl tryptamines; 5-HT 6 ligands; binding affinity; combinatorial protocol in multiple linear regression (CP-MLR).