Novel ZE-isomerism descriptors derived from molecular topology and their application to QSAR analysis.
We introduce several series of novel ZE-isomerism descriptors derived directly from two-dimensional molecular topology. These descriptors make use of a quantity named ZE-isomerism correction, which is added to the vertex degrees of atoms connected by double bonds in Z and E configurations. This approach is similar to the one described previously for topological chirality descriptors (Golbraikh, A., et al. J. Chem. Inf. Comput. Sci. 2001, 41, 147-158). The ZE-isomerism descriptors include modified molecular connectivity indices, overall Zagreb indices, extended connectivity, overall connectivity, and topological charge indices. They can be either real or complex numbers. Mathematical properties of different subgroups of ZE-isomerism descriptors are discussed. These descriptors circumvent the inability of conventional topological indices to distinguish between Z and E isomers. The applicability of ZE-isomerism descriptors to QSAR analysis is demonstrated in the studies of a series of 131 anticancer agents inhibiting tubulin polymerization.
Laboratory for Molecular Modeling, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Alexander
A
Golbraikh
Danail
D
Bonchev
Alexander
A
Tropsha
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D008433:Mathematics; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010600:Pharmacology; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001704:Biopolymers; D004364:Pharmaceutical Preparations; D013267:Stilbenes; D014404:Tubulin