Structure activity relationship study of the beta-lactamase inhibitors and theoretical design for new bioactive compounds

Author(s)

Granato, Ana Claudia ; Costae, Edson B. ; Barboza, Marlei ; Trsic, Milan ; MendezVilas, A

• Document type: Journal article
• Source: MICROORGANISMS IN INDUSTRY AND ENVIRONMENT: FROM SCIENTIFIC AND INDUSTRIAL RESEARCH TO CONSUMER PRODUCTS; v. N/A, p. 6-pg., 2011-01-01.

Abstract

Theoretical calculations for the beta-lactamase inhibitors Clavulanic Acid (CA), Tazobactam (T) and Sulbactam (S), were performed with the purpose to assessing which properties may correlate with the biological activity presented in the literature. The results obtained suggests that the GAP(HOMO-LUMO), the molecular hardness (eta) and the hyperpolarizability (beta) display reasonable correlations with the P-lactamase inhibitor activity of the compounds. For comparison the inactive isomers of Clavulanic Acid were also studied. The molecular and electronic properties of various proposed beta-lactamase inhibitors were calculated and the structures search planning was based in the structures of CA, T and S, the beta-lactamase inhibitors in clinical. Some hypothetical compounds with a significant improvement in calculated indicators are presented. These hypothetical molecules could be a synthetic alternatives to be employed as beta-lactamase inhibitors. (AU)

• FAPESP's process: 05/55079-4 - Production and purification of clavulanic acid, cephamycin C and other bioactive metabolites of Streptomyces
• Grantee: Carlos Osamu Hokka
• Support Opportunities: Research Projects - Thematic Grants