Cytotoxic Cyclotides from Anchietea pyrifolia, a South American Plant Species

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Fernandez-Bobey, Antonio ; Ferreira Pinto, Meri Emili ; de Almeida, Larissa Costa ; de Souza, Bibiana Monson ; Dias, Nathalia Baptista ; De Paula-Souza, Juliana ; Cilli, Eduardo Maffud ; Lopes, Norberto Peporine ; Costa-Lotufo, Leticia Veras ; Palma, Mario Sergio ; Bolzani, Vanderlan da Silva

• Document type: Journal article
• Source: Journal of Natural Products; v. 85, n. 9, p. 8-pg., 2022-08-31.

Abstract

Cyclotides are mini-proteins with potent bioactivities and outstanding potential for agricultural and pharmaceutical applications. More than 450 different plant cyclotides have been isolated from six angiosperm families. In Brazil, studies involving this class of natural products are still scarce, despite its rich floristic diversity. Herein were investigated the cyclotides from Anchietea pyrifolia roots, a South American medicinal plant from the family Violaceae. Fourteen putative cyclotides were annotated by LC-MS. Among these, three new bracelet cyclotides, anpy A-C, and the known cycloviolacins O4 (cyO4) and O17 (cyO17) were sequenced through a combination of chemical and enzymatic reactions followed by MALDI-MS/MS analysis. Their cytotoxic activity was evaluated by a cytotoxicity assay against three human cancer cell lines (colorectal carcinoma cells: HCT 116 and HCT 116 TP53(-/-) and breast adenocarcinoma, MCF 7). For all assays, the IC50 values of isolated compounds ranged between 0.8 and 7.3 mu M. CyO17 was the most potent cyclotide for the colorectal cancer cell lines (IC50, 0.8 and 1.2 mu M). Furthermore, the hemolytic activity of anpy A and B, cyO4, and cyO17 was assessed, and the cycloviolacins were the least hemolytic (HD50 > 156 mu M). This work sheds light on the cytotoxic effects of the anpy cyclotides against cancer cells. Moreover, this study expands the number of cyclotides obtained to date from Brazilian plant biodiversity and adds one more genus containing these molecules to the list of the Violaceae family. (AU)

• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 19/04381-5 - The Last Advances on Solid-Phase Peptide Synthesis and NMR New Methodologies Applied to Cyclotides from Brazilian Plant Species
• Grantee: Meri Emili Pinto Nascimento
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 20/02207-5 - Inventorying secondary metabolism applying metabolomic strategies: contribution to the Brazilian biodiversity valuation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 14/25222-9 - Vibrational chiroptical spectroscopy for stereochemical characterization of small molecules and macromolecules
• Grantee: João Marcos Batista Junior
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/26550-3 - Cyclic peptides from brazilian plants: isolation, structural characterization, synthesis, and evaluation of biological activities
• Grantee: Antonio Fernández Bobey
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/17098-4 - Application of MALDI Imaging (MSI) on non-nodulated and nodulated leaves of Psychotria and Hybanthus: Localization, analysis of cyclotides and its relationship with endosymbionts bacteria
• Grantee: Meri Emili Pinto Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/16212-5 - Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays
• Grantee: Mario Sergio Palma
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants