Topological pattern for the search of new active drugs against methicillin resistant Staphylococcus aureus.

Topological pattern for the search of new active drugs against methicillin resistant Staphylococcus aureus. Eur J Med Chem. 2017 Jul 08;138:807-815 Authors: Bueso-Bordils JI, Perez-Gracia MT, Suay-Garcia B, Duart MJ, Martin Algarra RV, Lahuerta Zamora L, Anton-Fos GM, Aleman Lopez PA Abstract Molecular topology was used to develop a mathematical model capable of classifying compounds according to antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA). Topological indices were used as structural descriptors and their relation to antimicrobial activity was determined by using linear discriminant analysis. This topological model establishes new structure activity relationships which show that the presence of cyclopropyl, chlorine and ramification pairs at a distance of two bonds favor this activity, while the presence of tertiary amines decreases it. This model was applied to a combinatorial library of a thousand and one 6-fluoroquinolones, from which 117 theoretical active molecules were obtained. The compound 10 and five new quinolones were tested against MRSA. They all showed some activity against MRSA, although compounds 6, 8 and 9 showed anti-MRSA activity similar to ciprofloxacin. This model was also applied to 263 theoretical antibacterial agents described by us in a previous work, from which 34 were predicted as theoretically active. Anti-MRSA activity was found bibliographically in 9 of them (ensuring...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research