Evaluation of the antimicrobial activity of curcuminoids and study of their gas phase fragmentation reactions by sequential mass spectrometry

Author(s)

Tatiana Manzini Vieira

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-03-15

Examining board members

Luiz Alberto Beraldo de Moraes; Vladimir Constantino Gomes Heleno; Antonio Gustavo Sampaio de Oliveira Filho; Marcos Pivatto

• Advisor: Antonio Eduardo Miller Crotti

Abstract

In this work, a series of monoketone curcuminoids were synthesized by condensation between acetone, and 11 (eleven) different aromatic aldehydes. These curcuminoids were subsequently converted to their corresponding saturated alcohols and ketones by means of catalytic hydrogenation reactions. The obtained compounds were evaluated for their antimicrobial activities against a representative panel of cariogenic bacteria using microdilution plating method. In addition, the gas-phase fragmentation pathways of the protonated monoketone curcuminoids were investigated by ionization tandem mass spectrometry (ESI-MS/MS) in combination with accurate mass data, multi-stage mass spectrometry (MSn), and deuterium exchange experiments, as well as in thermochemical data estimated by Computational Chemistry. Among the 31 curcuminoids evaluated, curcumin A (10), (1E,4E)-1,5-bis(4-hydroxyphenyl)penta-1,4-dien-3-one, and (1E,4E)5-bis(4-hydroxyphenyl)penta-1,4-dien-3-one (11) showed the most effective antimicrobial activity, with minimum inhibitory concentration (MIC) values of 50 g/mL against Streptococcus mutans and 50 g/mL against Streptococcus mitis. MIC values of curcumin A (10) were lower than the previously reported MIC values for its -diketone analog of compound 10. The inferred structure-activity relationships indicated that the hydroxyl group attached to the aromatic rings and the double bond between C2-C3 and C2\'-C3 \'and the carbonyl group and C1 are the characteristics responsible for the antimicrobial activity. The results showed that the ion H and the acylium ion D, resulting from two competitive hydrogen rearrangements, are the most intense in the spectrum of proton curcuminoids product ions. Besides the identification of some diagnostic ions, this work proved that the formation of some product ions occured from an intermediate ion resulting from a Nazarov cyclization of the protonated molecule, whose occurrence has been previously reported in the literature. The thermochemical data supported the structures of the proposed ions and showed that the position of the phenolic hydroxyl in the aromatic ring plays a key role in the Nazarov cyclization. The results of this work may contribute in future to the identification of products from the in vitro and in vivo metabolism studies without the need for standards or isolation of these metabolites (AU)

• FAPESP's process: 16/19272-9 - Evaluation of the antimicrobial activity of curcuminoids and study of their fragmentation reactions in the gas-phase by tandem mass spectrometry
• Grantee: Tatiana Manzini Vieira
• Support Opportunities: Scholarships in Brazil - Master