In vitro studies of bioaccessibility, intestinal transportation and biotransformation of ent-hardwickiic and ent-polyalthic acids from Copaifera pubiflora and Copaifera duckei oil resins

• Grant number: 16/25201-7
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2017
• End date: August 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Niege Araçari Jacometti Cardoso Furtado
• Grantee: Niege Araçari Jacometti Cardoso Furtado
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The studies proposed in this project of bioaccessibility, intestinal transportation and biotransformation of diterpenes that are constituents of Copaifera sp. oil resins are new in this research field and it is hoped to bring knowledge that will contribute to the more efficient and safe use of this vegetal raw material. One of the major bottlenecks of Brazilian research is the lack of studies of absorption, distribution, metabolism and excretion of natural bioactive compounds, which would facilitate the implementation of some phases of preclinical studies. The population has free and easy access to the medicinal use of several species of Copaifera, and complex matrices, such as oil resins from Copaifera species, may play an important role in the bioaccessibility and absorption of diterpenes. Therefore, the aim of this project is to carry out bioaccessibility studies of the major diterpenes ent-hardwickiic and ent-polyalthic acids from Copaifera pubiflora and Copaifera duckei oil resins, respectively, as well as to evaluate the influence of digestive conditions of the upper gastrointestinal tract in the bioaccessibility of diterpenes. It will be considered all the digestion steps that precede the absorption (salivary, gastric and duodenal abiotic). In this project, it is also intended to carry out studies to evaluate the intestinal absorption of diterpenes in Caco-2 cell models and to investigate the possible intestinal metabolism of diterpenes. In addition, biotransformation processes of diterpenes will be developed using bacteria from the intestinal microbiota and filamentous fungi in order to select one or two promising processes to isolate and elucidate the chemical structures of the major biotransformation products. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOUSA, INGRID P.; DE SOUSA TEIXEIRA, MARIA, V; FREITAS, JOLINDO A.; FERREIRA, ANTONIO G.; PIRES, LOREN M.; SANTOS, RAQUEL A.; GOMES HELENO, VLADIMIR CONSTANTINO; CARDOSO FURTADO, NIEGE A. JACOMETTI. Production of More Potent Anti-Candida Labdane Diterpenes by Biotransformation Using Cunninghamella elegans. CHEMISTRY & BIODIVERSITY, v. 19, n. 3, p. 9-pg., 2022-02-19. (11/13630-7, 16/25201-7)

CRUZ DE CARVALHO, TATIANE; DE OLIVEIRA SILVA, ELIANE; SOARES, GILBERTO AUGUSTO; PARREIRA, RENATO LUIS TAME; AMBROSIO, SERGIO RICARDO; JACOMETTI CARDOSO FURTADO, NIEGE ARACARI. Fungal biocatalysts for labdane diterpene hydroxylation. Bioprocess and Biosystems Engineering, v. 43, n. 6, FEB 2020. (11/13630-7, 16/25201-7, 12/01766-4)

LOUREIRO DAMASCENO, JOAO PAULO; DA ROSA, HEMERSON SILVA; DE ARAUJO, LUCIANA SILVA; JACOMETTI CARDOSO FURTADO, NIEGE ARACARI. Andrographis paniculata Formulations: Impact on Diterpene Lactone Oral Bioavailability. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, v. 47, n. 1, NOV 2021. (16/25201-7, 17/16012-9)

DE SOUSA, INGRID PONTES; FERREIRA, ANTONIO GILBERTO; MILLER CROTTI, ANTONIO EDUARDO; DOS SANTOS, RAQUEL ALVES; KIERMAIER, JOSEF; KRAUS, BIRGIT; HEILMANN, JOERG; JACOMETTI CARDOSO FURTADO, NIEGE ARACARI. New antifungal ent-labdane diterpenes against Candida glabrata produced by microbial transformation of ent-polyalthic acid. BIOORGANIC CHEMISTRY, v. 95, JAN 2020. (11/13630-7, 16/25201-7)

DE SOUSA, INGRID P.; SOUSA TEIXEIRA, MARIA V.; JACOMETTI CARDOSO FURTADO, NIEGE A.. An Overview of Biotransformation and Toxicity of Diterpenes. Molecules, v. 23, n. 6, JUN 2018. (16/25201-7)

SOUSA TEIXEIRA, M., V; FERNANDES, L. M.; DE PAULA, V. STEFANELLI; FERREIRA, A. G.; JACOMETTI CARDOSO FURTADO, N. A.. Ent-hardwickiic acid from C. pubiflora and its microbial metabolites are more potent than fluconazole in vitro against Candida glabrata. Letters in Applied Microbiology, v. 74, n. 4, p. 8-pg., 2022-01-17. (11/13630-7, 16/25201-7, 17/20397-3, 17/20071-0)