Generating new iboga-type alkaloids in Tabernaemontana litoralis

• Grant number: 20/03376-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2020
• End date: December 31, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Adriana Aparecida Lopes
• Grantee: Lyamara Mendonça de Souza Oliveira
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil

Abstract

Plants, microorganisms and insects biosynthesize small complex molecules, called "natural products". For our purposes, this means that these metabolites are a rich resource for a wide range of applications, including the development of pharmaceuticals, insecticides, herbicides, biomaterials and sources of bioenergy. Secondary metabolites called "alkaloids" are promising agents in the face of biological tests and are produced by a wide range of plants and insects. A group of alkaloids called "iboga-type alkaloids" are interesting because they show several biological activities such as; antioxidant, enzymatic, antitumor and cytotoxic inhibition, anti-inflammatory, antinociceptive, neuropharmacological, cardiovascular, antiprotozoal, antimicrobial, antibacterial, antifungal and antiviral. The species Tabernaemontana catharinensis A. DC. is a Brazilian medicinal species that biosynthesizes iboga-type alkaloids such as hydroxy-voacangin indoline and rupicoline, and which inhibit the enzyme acetylcholinesterase (AChE) in the same concentration (0.01 mM) of the two AChE inhibitors currently used in therapy Alzheimer's disease (galanthamine and physostigmine). In addition, the species Tabernaemontana litoralis also presents indole alkaloids, 18-hydroxipseudovincadiformine, coronaridine, heyneanine and 3,19-oxocoronaridine the major compounds. We know that a new chemical diversity opens up many possibilities for new biological activities. Therefore, the objective of this research project is to generate new analogs of chlorinated iboga-type alkaloids using the precursor-directed biosynthesis approach(BDP) using Tabernaemontana litoralis. Obtaining new chlorinated analogues can generate even more biologically active molecules than own natural alkaloid. (AU)