Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


Importance of Kier-Hall Topological Indices in the QSAR of Anticancer Drug Design

Author(s): Sisir Nandi, Manish C. Bagchi.


An important area of theoretical drug design research is quantitative structure activity relationship (QSAR) using structural invariants. The impetus for this research trend comes from various directions. Researchers in chemical documentation have searched for a set of invariants which will be more convenient than the adjacency matrix (or connection table) for the storage and comparison of chemical structures [1]. Molecular structure can be looked upon as the representation of the relationship among its various constituents. The term molecular structure represents a set of nonequivalent and probably disjoint concepts [2]. There is no reason to believe that when we discuss diverse topics (e.g. chemical synthesis, reaction rates, spectroscopic transitions, reaction mechanisms, and ab initio calculations) using the notion of molecular structure, the different meanings we attach to the single term molecular structure originate from the same fundamental concept. On the contrary, there is a theoretical and philosophical basis for the non-homogeneity of concepts covered by the term molecular structure.

In the context of molecular science, the various concepts of molecular structure (e.g. classical valence bond representations, various chemical graph-theoretic representations, ball and spoke model of a molecule, representation of a molecule by minimum energy conformation, semi symbolic contour map of a molecule, or symbolic representation of chemical species by Hamiltonian operators) are model objects [3] derived through different abstractions of the same chemical reality. In each instance, the equivalence class (concept or model of molecular structure) is generated by selecting certain aspects while ignoring some unique properties of those actual events. This explains the plurality of the concept of molecular structure and their autonomous nature, the word autonomous being used in the same sense that one concept is not logically derived from the other.

At the most fundamental level, the structural model of an assembled entity (e.g. a molecule consisting of atoms) may be defined as the pattern of relationship among its parts as distinct from the values associated with them [4].

Constitutional formulae of molecules are graphs where vertices represent the set of atoms and edges represent chemical bonds [5]. The pattern of connectedness of atoms in a molecule is preserved by constitutional graphs. A graph (more correctly a non-directed graph) G = [V, E] consists of a finite non-empty set V of points together with a prescribed set E of unordered pairs of distinct points of V [6]. Thus the mathematical characterization of structures represents structural invariants having successful applications in chemical documentation, characterization of molecular branching, enumeration of molecular constitutional associated with a particular empirical formula, calculation of quantum chemical parameters for the generation of quantitative structure-property-activity correlations [7]. Kier developed a number of structural invariants which are now-a-days called as topological indices with wide range of practical applications for QSAR and drug design. The present paper is restricted to the review of Kier-Hall topological indices for QSAR and anticancer drug design for 2,5-bis(1-aziridinyl) 1,4-benzoquinone (BABQ) [8], pyridopyrimidine [9], 4-anilinoquinazoline [10] and 2-Phenylindoles [11] compounds utilizing various statistical multivariate regression analyses.

Keywords: QSAR, Kier-Hall topological descriptors, BABQ, pyridopyrimidine, 4-anilinoquinazolines, 2-phenylindoles, partial least square, ridge regression, anticancer drug design, topological indices

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Article Details

Year: 2012
Page: [159 - 170]
Pages: 12
DOI: 10.2174/157340912800492384
Price: $58