Title: Fourth generation detour matrix-based topological indices for QSAR/QSPR - Part-1: development and evaluation

Authors: Rakesh Kumar Marwaha; Harish Jangra; Kinkar C. Das; P.V. Bharatam; A.K. Madan

Addresses: Faculty of Pharmaceutical Sciences, M.D. University, Rohtak 124-001, India. ' Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160-062, India. ' Department of Mathematics, Sungkyunkwan University, Suwon 440-746, South Korea. ' Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali 160-062, India. ' Faculty of Pharmaceutical Sciences, Pt. B.D. Sharma University of Health Sciences, Rohtak 124-001, India

Abstract: In the present study, four detour matrix-based Topological Indices (TIs) termed as augmented path eccentric connectivity indices 1-4 (denoted by ^APξ₁^C, ^APξ₂^C, ^APξ₃^C and ^APξ₄^C) as well as their topochemical versions (denoted by ^APξ_1c^C, ^APξ_2c^C, ^APξ_3c^C and ^APξ_4c^C) have been conceptualised. A modified detour matrix termed as chemical detour matrix (Δ_c) has also been proposed so as to facilitate computation of index values of topochemical versions of the said TIs. Values of the proposed TIs were computed for all the possible structures containing three, four and five vertices using an in-house computer program. The said TIs exhibited exceptionally high discriminating power and high sensitivity towards branching/relative position of substituent(s) in cyclic structures amalgamated with negligible degeneracy. Due care was taken during the development of TIs so as to ensure that reduction in index values of complex chemical structures to be within reasonable limits without compromising discriminating power. The mathematical properties of one of the proposed TIs have also been studied. With exceptionally high discriminating power, high sensitivity towards branching as well as relative position(s) of substituents in cyclic structures and negligible degeneracy, the proposed indices offer a vast potential for use in characterisation of structures, similarity/dissimilarity studies, lead identification and optimisation, combinatorial library design and quantitative structure-activity/property/toxicity/pharmacokinetic relationship studies.

Keywords: path eccentricity; chemical detour matrix; chemical path; Wiener index; Balaban index; Randic molecular connectivity index; eccentric connectivity index; computational chemistry; topological indices; structure activity-property relationship; toxicity; pharmacokinetics; similarity-dissimilarity; lead identification; optimisation; chemical structures.

DOI: 10.1504/IJCBDD.2012.049201

International Journal of Computational Biology and Drug Design, 2012 Vol.5 No.3/4, pp.335 - 360

Received: 09 Jan 2012
Accepted: 02 May 2012
Published online: 05 Dec 2014 *

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