Oxindole alkaloids from Uncaria tomentosa: biosynthetic studies and alkaloids analogues obtained by precursor-directed biosynthesis

• Grant number: 13/07349-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Adriana Aparecida Lopes
• Grantee: Adriana Aparecida Lopes
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated researchers: Ana Maria Soares Pereira ; Maysa Furlan ; Norberto Peporine Lopes ; Suzelei de Castro França
• Associated research grant(s): 16/50463-5 - Exclusive production of fluoro-unnatural oxindole alkaloids by transgenic Uncaria guianensis via precursor-directed biosynthesis, AP.R SPRINT; 15/26066-3 - Mevalonate-derived quinonemethide triterpenoid from in vitro roots of Peritassa laevigata and their localization in root tissue by MALDI imaging, PUB.ART
• Associated scholarship(s): 18/17324-7 - Obtaining new benzofuran-derived alkaloids using precursor-directed biosynthesis in Uncaria tomentosa, BP.IC; 17/04645-7 - Production of methylated oxindole alkaloids analogues by precursor-directed biosynthesis using Uncaria tomentosa species, BP.IC; 16/18799-3 - Chemical and molecular (cDNA - SRAP) approaches from precursor-directed biosynthesis experiments in Uncaria guianensis, BP.IC; + associated scholarships 15/18978-2 - Production of methylated oxindole alkaloid analogues by precursor-directed biosynthesis using in vitro Uncaria guianensis, BP.IC; 15/18339-0 - Fluorinated analogues of pentacyclic oxindole alkaloids optimization production by precursor-directed biosynthesis using Uncaria guianensis in vitro, BP.IC; 13/22609-7 - Oxindole alkaloids from Uncaria tomentosa: biosynthetic studies and alkaloids analogues obtained by precursor-directed biosynthesis, BP.JP - associated scholarships

Abstract

Natural products and their derivatives represent one of the successful alternatives in the discovery of new drugs. Among some of the main approaches to diversify the structure of a natural product are the semi-synthesis and the biotransformation. Another way to diversify the biosynthesis of natural products is related to direct or indirect modifications in the organism, through the addition of unnatural precursors in the culture medium, called precursor-directed biosynthesis. This research project considers the use of precursor-directed biosynthesis to obtain oxindole alkaloids analogues that display important anti-tumoral properties, using "in vitro" micropropagation of Uncaria tomentosa (Rubiaceae). The vegetal culture medium will be supplemented with different tryptophan analogues, the important indolic precursor of the biosynthetic route of pentaciclic oxindole alkaloids (AOP). Information about AOP biosynthesis is essential for the knowledge of the involved biosynthetic pathways. This way, studies using enriched precursors, in case 1-13C-D-glucose, are important for the knowledge of the biosynthetic pathways, specially the terpenoid pathway that can occur by mevalonate (MVA) and/or 1-deoxy-D-xylulose 5-phosphate pathways (MEP). All oxindole alkaloids analogues obtained by precursor-directed biosynthesis, as well as the natural alkaloids, will be submitted to the evaluation of anti-tumoral and anti-inflammatory activities. Therefore, this project aims to implement a new interdisciplinary research field in Biosynthesis in the Departamento de Biotecnologia Vegetal da Universidade de Ribeirão Preto (UNAERP). The consolidation of this proposal must be achieved by using precursor-directed biosynthesis in order to obtain oxindolic alkaloids analogues from Uncaria tomentosa, which will be evaluated in anti-tumoral and anti-inflammatory assays aiming to widen the therapeutic options. (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)

PINA, EDIEIDIA S.; SILVA, DENISE B.; TEIXEIRA, SIMONE P.; COPPEDE, JULIANA S.; FURLAN, MAYSA; FRANCA, SUZELEI C.; LOPES, NORBERTO P.; PEREIRA, ANA MARIA S.; LOPES, ADRIANA A.. Mevalonate-derived quinonemethide triterpenoid from in vitro roots of Peritassa laevigata and their localization in root tissue by MALDI imaging. SCIENTIFIC REPORTS, v. 6, MAR 4 2016. (09/54098-6, 14/50265-3, 12/18031-7, 13/07349-9, 15/26066-3, 10/18132-2)

LOPES, ADRIANA A.; CHIOCA, BIANCA; MUSQUIARI, BRUNO; CREVELIN, EDUARDO J.; FRANCA, SUZELEI DE C.; FERNANDES DA SILVA, MARIA FATIMA DAS G.; PEREIRA, ANA MARIA S.. Unnatural spirocyclic oxindole alkaloids biosynthesis in Uncaria guianensis. SCIENTIFIC REPORTS, v. 9, AUG 5 2019. (13/22609-7, 15/18978-2, 13/07349-9)