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Preparation and Biological Evaluation of Curcumin-Cinnamaldehyde Hybrids as Bacterial Cell Division Inhibitors Dehydrozingerone Derivatives (Part II)

Grant number: 16/07108-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2016
Effective date (End): December 31, 2016
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Luis Octávio Regasini
Grantee:Gabriela Miranda Ayusso
Host 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


Anti-infective agents are crucial drugs for life expectancy. Several reasons justify the need for new antibacterials, including high bacterial resistance and high mortality caused by infectious diseases. Thus, efforts are need to develop innovative antibacterial drugs. Recently, curcumin and cinnmaldehyde exhibited potent antibacterial activity. 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), which is a vital macromolecule for all bacteria. The current project purposes the synthesis of two series of curcumin-cinnamaldehyde hybrid, which are dehydrozingerone derivatives. These compounds will be prepared by aldol condensation reactions between ketone derivatives and aldehydes, under basic catalysis. 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. Hybrids displayed IS e 10 will be submitted to inhibitory bacterial cell division assays, using FtsZ sedimentation and GTP hydrolysis methods.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MORAO, LUANA G.; LORENZONI, ANDRE S. G.; CHAKRABORTY, PARICHITA; AYUSSO, GABRIELA M.; CAVALCA, LUCIA B.; SANTOS, MARIANA B.; MARQUES, BEATRIZ C.; DILARRI, GUILHERME; ZAMUNER, CAIO; REGASINI, LUIS O.; et al. Investigating the Modes of Action of the Antimicrobial Chalcones BC1 and T9A. Molecules, v. 25, n. 20, . (16/07108-0, 17/50216-0, 14/18577-5, 14/18330-0, 18/15083-2, 16/08084-7, 14/18719-4)

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