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Preparation and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors: Methoxychalcones

Grant number: 14/18577-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2014
Effective date (End): September 30, 2015
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Luis Octávio Regasini
Grantee:Beatriz de Carvalho Marques
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Antibacterial agents are crucial drugs for life expectancy. Several reasons justify the need by new antibacterials, including high bacterial resistance and mortality caused by infectious diseases. Thus, efforts are urgent to develop innovative antibacterial drugs. Recently, curcumin and cinnmaldehyde exhibited potent antibacterial activity against a broad panel of fungi. The central interest by these natural products is related to their bacterial cell division inhibitory effect, and their interaction with FtsZ protein (filamentous temperature-sensitive protein Z), a vital macromolecule for all bacteria. The current project purposes the preparation of two series of compounds. The series I and II will be constitute by chalcones substituted with methoxyl group (s) at rings A and B, respectively. Compounds from series A an B were designed by molecular hybridization, using curcumin and cinnamaldehyde as prototypes. Compounds will be prepared by aldol condensation reactions. Compounds will be tested against Gram-positive, Gram-negative bacteria and Mycobacterium species, using sensitive and resistant strains. The toxicity of selected antibacterial compounds will be evaluated on macrophages. The selective index (SI) of compounds will be calculated from IC50 and MBC values, SI = IC50/MBC. IC50 is a half maximal inhibitory concentration to kill macrophages and MBC is a minimum bactericidal concentration. Compounds displayed IS e 10 will be submitted to inhibitory bacterial cell division assays, using FtsZ sedimentation and GTP hydrolysis methods. The chemical data obtained previously by the applicant and the insertion of the project in the Agreement for Scientific and Technological Cooperation between FAPESP and NWO (Netherlands Organization for Scientific Research)FAPESP 2013/50678-3 corroborate the feasibility and the internationalization proposal.