Evaluation of the antibacterial and antiparasitic activities of artepillin C and its prenylated analogs and study of their gas-phase fragmentation reactions using tandem mass spectrometry

Author(s)

Tatiana Manzini Vieira

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC)
• Defense date: 2023-09-15

Examining board members

Antonio Eduardo Miller Crotti; Niege Araçari Jacometti Cardoso Furtado; Vladimir Constantino Gomes Heleno; Carlos Henrique Gomes Martins

• Advisor: Antonio Eduardo Miller Crotti

Abstract

Artepillin C is one of the main components of true propolis. Several biological activities have been attributed to artepilin C, and the antimicrobial activity has been highlighted. In this work, artepillin C and 14 prenylated analogues and their derivatives were synthesized and evaluated for their antibacterial, schistosomicidal and leishmanicidal activities. Furthermore, the gas phase fragmentation reactions of the synthesized compounds were investigated by sequential electrospray ionization mass spectrometry (ESI-MS/MS). Although the use of microwave irradiation reduced the time of prenylation step of methyl p-coumaroate from 24 h to 10 min, it was not possible to avoid the formation of three prenylated by-products, which had also been formed under conditions in the literature. None of the 15 compounds synthesized showed promising schistosomal against adult Schistosoma mansoni worms or leishmanicidal activity against Leishmania amazonensis promastigote forms. On the other hand, compounds 5 (plicatin B) and 6 (2\',3\',7\',8\'- dihydroplicatin B) showed promising antibacterial activity against a representative panel of cariogenic bacteria, with minimum inhibitory concentration (MIC) values between 32.2 and 62.5 µg/mL. Data obtained by molecular docking demonstrated that compounds 5 and 6 meet all the physicochemical, pharmacokinetic, and bioavailability criteria to be considered as promising. Mass spectrometry studies showed that C-prenylated compounds can be differentiated from O-prenylated compounds by the losses of C4H8 and C5H8, respectively. Moreover, the use of multiple reaction monitoring (MRM) scan mode based on the transitions 301→259, 301→245 and 301→203 for artepillin C (5) and 247→205, 247→191, and 247→159 for plicatin B (6) allowed for the identification of these compounds in a commercial sample of green propolis using ultra-performance chromatography coupled with sequential mass spectrometry with ionization by electrospray (UPLC-ESI-MS/MS). (AU)

• FAPESP's process: 19/11700-0 - Evaluation of the antimicrobial and antiparasitic activities of Artepillin C and its derivatives and study of their gas-phase fragmentation reactions using tandem mass spectrometry
• Grantee: Tatiana Manzini Vieira
• Support Opportunities: Scholarships in Brazil - Doctorate