Estudos da relação estrutura-atividade dos derivados análogos da cumarina contra as bactérias Staphylococcus aureus e a Escherichia coli

Abstract

Coumarin is the subject of frequent investigations of pharmacological interest. Among the characteristics that make coumarin such a relevant substance are its abundant natural origin, low cost, stable compound, and various conformations. This diversity of conformations enables its derivatives to present biological activities of anticoagulant, immunosuppressive, vasodilatory, muscle relaxant, antithrombotic, hypotensive, antibacterial action, among others. Twelve analogous derivatives of 3- [3-phenyl-3- (phenylamino) propanoyl] -2H-chromen-2-one, synthesized from coumarin for the evaluation of their antibacterial activity for Staphylococcus aureus and Escherichia coli. According to data from the Ministry of Health, Staphylococcus aureus is responsible for 7.7% of foodborne outbreaks nationwide. Escherichia coli is responsible for causing enterohemorrhagic diseases characterized by severe abdominal cramps and severe diarrhea, including the presence of blood. In molecular modeling, mathematical models were used with the theory of density functional. Calculations were performed using the M062X hybrid exchange and correlation functional and using the 6-311 ++ G (d, p) base set. The statistical treatment used was the principal component analysis. Descriptors capable of separating the 12 compounds into active and inactive for both bacteria were defined. For Staphylococcus aureus the descriptors selected to separate the active and inactive compounds were the carbon atomic charges 18 and 23 and the binding order between carbon 24 and hydrogen 44. For Escherichia coli the selected descriptors were the binding angle between atoms 22, 25 and 24, the energy of the HOMO boundary orbital and the bonding angle between atoms 8, 13 and 15.