Antibacterial activity of 3,3 '-dihydroxycurcumin (DHC) is associated with membrane perturbation

Author(s):Show less -

Polaquini, Carlos R. ; Morao, Luana G. ; Nazare, Ana C. ; Torrezan, Guilherme S. ; Dilarri, Guilherme ; Cavalca, Lucia B. ; Campos, Debora L. ; Silva, Isabel C. ; Pereira, Jesse A. ; Scheffers, Dirk-Jan ; Duque, Cristiane ; Pavan, Fernando R. ; Ferreira, Henrique ; Regasini, Luis O.

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 90, p. 8-pg., 2019-09-01.

Abstract

Curcumin is a plant diphenylheptanoid and has been investigated for its antibacterial activity. However, the therapeutic uses of this compound are limited due to its chemical instability. In this work, we evaluated the antimicrobial activity of diphenylheptanoids derived from curcumin against Gram-positive and Gram-negative bacteria, and also against Mycobacterium tuberculosis in terms of MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values. 3,3'-Dihydroxycurcumin (DHC) displayed activity against Enterococcus faecalis, Staphylococcus aureus and M. tuberculosis, demonstrating MIC values of 78 and 156 mu g/mL. In addition, DHC was more stable than curcumin in acetate buffer (pH 5.0) and phosphate buffer (pH 7.4) for 24 h at 37 degrees C. We proposed that membrane and the cell division protein FtsZ could be the targets for DHC due to that fact that curcumin exhibits this mode of antibacterial action. Fluorescence microscopy of Bacillus subtilis stained with SYTO9 and propidium iodide fluorophores indicated that DHC has the ability to perturb the bacterial membrane. On the other hand, DHC showed a weak inhibition of the GTPase activity of B. subtilis FtsZ. Toxicity assay using human cells indicated that DHC has moderate capacity to reduce viability of liver cells (HepG2 line) and lung cells (MRC-5 and A549 lines) when compared with doxorubicin. Alkaline comet assay indicated that DHC was not able to induce DNA damage in A549 cell line. These results indicated that DHC is promising compound with antibacterial and antitubercular activities. (AU)

• FAPESP's process: 09/53989-4 - Acquisition of a nuclear magnetic resonance spectrometer for studies of biomolecules
• Grantee: Raghuvir Krishnaswamy Arni
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/50367-8 - New environmental-friendly compounds to combat citrus canker
• Grantee: Henrique Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/50162-2 - Protecting plants with antimicrobial peptides and gallates - Pro-Planta
• Grantee: Henrique Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/08089-6 - Preparation and biological evaluation of alkyl dihydroxybenzoates (AD) as useful agents to combat citrus canker
• Grantee: Ana Carolina Nazaré
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/50216-0 - Using agricultural waste to combat plant pathogens environmental friendly ways to combat Xanthomonas citri
• Grantee: Henrique Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50880-0 - INCT 2014: comparative and functional genomics and citrus-assisted breeding
• Grantee: Marcos Antonio Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/15083-2 - Synthesis and biological evaluation of isobavachalcone (IBC) and analogs as potential agents against tuberculosis
• Grantee: Luis Octávio Regasini
• Support Opportunities: Regular Research Grants