Prospecting for anticancer secondary metabolites produced by phytopathogenic fungi

• Grant number: 21/08535-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Effective date (Start): February 01, 2022
• Effective date (End): January 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: João Ernesto de Carvalho
• Grantee: Jaqueline Moraes Bazioli
• Supervisor: Joanna Burdette
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: University of Illinois at Chicago (UIC), United States
• Associated to the scholarship: 19/11563-2 - Prospecting for anticancer secondary metabolites produced by phytopathogenic fungi, BP.DD

Abstract

According to statistical data from 1946 to Sep/2019, there are 13.5% and 25.1% of anticancer drugs originating and derived from natural products, respectively. Epicoccum sp. is a genus of ubiquitous ascomycetes belongs to the Didymellaceae family and known to produce a wide variety of biologically and chemically useful compounds, such as polyketides, diketopiperazines, polyketide hybrids including pyridone alkaloid, tetramic acids and meroterpenoids. Our studies using in vitro assays have shown the potent antiproliferative activity of JB2.2 and JB2.3 fractions from Epicoccum sp., with remarkable selectivity for NCI/ADR-RES (multidrug-resistant ovarian tumor) and U251 (glioma) cell lines. Untargeted metabolomics was performed in GNPS (Global Natural Product Social Molecular Networking) leading to the annotation of 12 natural products and their analogues, in addition to compounds not yet reported for this species. After preliminary results of antiproliferative activity and bioguided fractionation, epipyridone compound (1.1 mg) was isolated from JB2.2 active fraction, exhibiting cytotoxicity with IC50-value of 61.66 ¼g/mL against the OVCAR-3 cell line, after 48 h treatment. Among future perspectives, we intend to investigate the mechanism of action of the JB2.2/JB2.3 fractions regarding cytotoxicity observed, in addition to in vivo tests in ovarian tumor models. To date, no secondary metabolites from Epicoccum sp. fungus have been studied in an in vivo system, which justifies the need for an exploratory analysis of this fungus. The proposed experiments will provide unprecedented data of its therapeutic potential with solid base for future clinical trials. (AU)

Scientific publications

(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)

KAWEESA, ELIZABETH N.; BAZIOLI, JAQUELINE M.; PIERRE, HERMA C.; LANTVIT, DANIEL D.; KULP, SAMUEL K.; HILL, KASEY L.; PHELPS, MITCH A.; COSS, CHRISTOPHER C.; FUCHS, JAMES R.; PEARCE, CEDRIC J.; et al. Exploration of Verticillins in High-Grade Serous Ovarian Cancer and Evaluation of Multiple Formulations in Preclinical In Vitro and In Vivo Models. MOLECULAR PHARMACEUTICS, v. 20, n. 6, p. 11-pg., 2023-05-08. (19/11563-2, 21/08535-7)