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The search for active substructures in structure‐activity studies
Author(s) -
Randić Milan,
JermanBlažič Borka,
Rouvray Dennis H.,
Seybold Paul G.,
Grossman Stuart C.
Publication year - 1987
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560320823
Subject(s) - substructure , fragment (logic) , graph , molecule , chemistry , stereochemistry , computational chemistry , computational biology , combinatorics , computer science , mathematics , algorithm , biology , organic chemistry , engineering , structural engineering
We consider the problem of location an active fragment (substructure) common to a class of biologically active compounds and presumed responsible for their biological activity (therapeutic or toxic). Our approach is graph‐theoretical in that molecules are represented by suitable graph‐theoretical invariants. Specially weighted paths in the molecular graph are adopted as descriptive elements. By selecting different sets of atoms one searches for a fragment that best represents the relative activities of the compounds. As an illustration we consider a dozen nitrosamine mutagens and analyze the cases of five‐, six‐, and sevenatom fragments. The approach clearly indicates that a specific seven‐atom fragment (for molecules with up to 11 nonhydrogen atoms) can account for the relative mutagenic activities of the nitrosamines considered.