Synthesis and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors

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 need 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 three series of curcumin-cinnamaldehyde hybrids. Series I and II/III composed by diphenylpentanoids and chalcones, respectively. These compounds will be prepared by conventional method, which employs aldol condensation reaction, under basic or acidic catalysis, using ethanol as solvent. 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, IS = 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. In addition, potent bacterial cell division inhibitors will be synthesized by environmental-friendly methods, including solvent-free reactions mechanically activated by grinding, and green solvents and-or green catalysts. (AU)