Antibacterial activity of a new monocarbonyl analog of curcumin MAC 4 is associated with divisome disruption

Author(s):Show less -

Polaquini, Carlos R. ^[1] ; Marques, Beatriz C. ^[1] ; Ayusso, Gabriela M. ^[1] ; Morao, Luana G. ^[2] ; Sardi, Janaina C. O. ^{[3, 4]} ; Campos, Debora L. ^[5] ; Silva, Isabel C. ^[5] ; Cavalca, Lucia B. ^{[6, 2]} ; Scheffers, Dirk-Jan ^[6] ; Rosalen, Pedro L. ^{[3, 7]} ; Pavan, Fernando R. ^[5] ; Ferreira, Henrique ^[2] ; Regasini, Luis O. ^[1]

Affiliation

^[1] Sao Paulo State Univ Unesp, Inst Biosci Humanities & Exact Sci, Dept Chem & Environm Sci, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Sao Paulo State Univ Unesp, Inst Biosci, Dept Biochem & Microbiol, BR-13050690 Rio Claro, SP - Brazil

^[3] Univ Campinas Unicamp, Piracicaba Dent Sch, Dept Physiol Sci, BR-13414903 Campinas, SP - Brazil

^[4] Fed Univ Mato Grosso do Sul Ufms, Sch Pharmaceut Sci Food & Nutr, BR-79070900 Campo Grande, MS - Brazil

^[5] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, BR-14800903 Araraquara, SP - Brazil

^[6] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Dept Mol Microbiol, NL-9747 AG Groningen - Netherlands

^[7] Fed Univ Alfenas Unifal, Sch Dent, BR-37130000 Alfenas, MG - Brazil

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 109, APR 2021.
• Web of Science Citations: 1

Abstract

Curcumin (CUR) is a symmetrical dicarbonyl compound with antibacterial activity. On the other hand, pharmacokinetic and chemical stability limitations hinder its therapeutic application. Monocarbonyl analogs of curcumin (MACs) have been shown to overcome these barriers. We synthesized and investigated the antibacterial activity of a series of unsymmetrical MACs derived from acetone against Mycobacterium tuberculosis and Gram-negative and Gram-positive species. Phenolic MACs 4, 6 and 8 showed a broad spectrum and potent activity, mainly against M. tuberculosis, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA), with MIC (minimum inhibitory concentration) values ranging from 0.9 to 15.6 mu g/mL. The investigation regarding toxicity on human lung cells (MRC-5 and A549 lines) revealed MAC 4 was more selective than MACs 6 and 8, with SI (selectivity index) values ranging from 5.4 to 15.6. In addition, MAC 4 did not demonstrate genotoxic effects on A549 cells and it was more stable than CUR in phosphate buffer (pH 7.4) for 24 h at 37 degrees C. Fluorescence and phase contrast microscopies indicated that MAC 4 has the ability to disrupt the divisome of Bacillus subtilis without damaging its cytoplasmic membrane. However, biochemical investigations demonstrated that MAC 4 did not affect the GTPase activity of B. subtilis FtsZ, which is the main constituent of the bacterial divisome. These results corroborated that MAC 4 is a promising antitubercular and antibacterial agent. (AU)

• FAPESP's process: 18/00163-0 - Development and search of new antimicrobials against Tuberculosis: from screening to pre-clinical studies in vivo
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• FAPESP's process: 14/18330-0 - Synthesis and biological evaluation of curcumin-cinnamaldehyde hybrids as bacterial cell division inhibitors
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