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

• Grant number: 14/18577-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2014
• End date: September 30, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Luis Octávio Regasini
• Grantee: Beatriz de Carvalho Marques
• 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

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.

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)

MARQUES, BEATRIZ C.; SANTOS, MARIANA B.; ANSELMO, DAIANE B.; MONTEIRO, DIEGO A.; GOMES, ELENI; SAIKI, MARILIA F. C.; RAHAL, PAULA; ROSALEN, PEDRO L.; SARDI, JANAINA C. O.; REGASINI, LUIS O.. Methoxychalcones: Effect of Methoxyl Group on the Antifungal Antibacterial and Antiproliferative Activities. Medicinal Chemistry, v. 16, n. 7, p. 881-891, 2020. (14/18330-0, 17/09245-7, 14/18577-5, 09/53989-4, 18/15083-2, 16/08084-7, 14/50926-0)

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, OCT 2020. (16/07108-0, 17/50216-0, 14/18577-5, 14/18330-0, 18/15083-2, 16/08084-7, 14/18719-4)