Isolation and identification of compounds from Melipona scutellaris geopropolis with antiproliferative and antiosteoclastogenic activities

Author(s)

Marcos Guilherme da Cunha

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2016-02-24

Examining board members

Pedro Luiz Rosalen; Severino Matias de Alencar; Masaharu Ikegaki; Ana Paula de Souza; Daniela Barretto Barbosa Trivella

• Advisor: Gilson Cesar Nobre Franco; Pedro Luiz Rosalen

Abstract

This study aimed to isolate and identify compounds from Melipona scutellaris geopropolis with antiproliferative and bone remodeling activities. Furthermore, we evaluated the pharmacokinetics and toxicological parameters of the major isolated compound, by in vitro and in silico methods. Geopropolis was collected in the city of Entre Rios, Bahia, northeastern Brazil (authorization CGEN # 010666/2014-1) and then the ethanol extract was prepared. The ethanol extract was successively fractionated and the biological activity of the generated fractions was evaluated by antiproliferative assay on colon cancer cell lines KM12 and COLO205. After isolation and identification of the active components in geopropolis, the major compound was evaluated for the following aspects: 1) inhibition of specific targets related to osteoclasts activation in bone remodeling process; 2) pharmacokinetic parameters predicted by in silico model; 3) genotoxicity determined by in vitro gene expression. The bioguided fractionation led to the isolation and identification of eight compounds with antiproliferative activity; seven coumarin derivatives and one benzophenone. Among the coumarins, two have not been described previously and were considered novelties. The major compound identified as a 4-phenyl coumarin and cinnamoyloxy-called mammeisin (CNM), although identified in plant source, has never been related to any biological activity. In this study, CNM was able to inhibit the activity of enzymes such as MMP-9 and TRAP, responsible for osteoclasts activation in the bone loss process. The pharmacokinetic parameters suggest low oral absorption, high plasma protein binding, low affinity for the main enzymes responsible for metabolism in the organism, but with mild to moderate potential toxicity to certain organs and tissues. Moreover, the compound showed low genotoxicity evidenced by up regulation of few genes related to DNA damage. Therefore, geopropolis has a different chemical profile compared to other propolis with coumarins identified as bioactive compounds, which have antiproliferative properties and activity on bone remodeling (AU)

• FAPESP's process: 11/23635-6 - Isolation and pharmacological evaluation of bioactive molecules from hexane fraction of M. scutellaris geopropolis
• Grantee: Marcos Guilherme da Cunha
• Support Opportunities: Scholarships in Brazil - Doctorate