Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Triterpenes and Alkaloids from Psychotria nuda (Cham. & Schltdl.) Wawra.

Almir De Carvalho Junior,Mario De Carvalho,Thatiana Ventura,Raimundo Braz-Filho,Elena Lassounskaia,Michel De Souza Passos,Rafaela Oliveira Ferreira,Sanderson Calixto,Samyra Da Silva Boeno,Ivo Curcino Vieira,Lorena Glória Das Virgens

doi:10.3390/molecules24061026

Abstract

A phytochemical study of leaves and twigs of Psychotria nuda resulted in 19 compounds, including five indole alkaloids, N,N,N-trimethyltryptamine, lyaloside, strictosamide, strictosidine, and 5α-carboxystrictosidine; two flavonolignans, cinchonain Ia and cinchonain Ib; an iridoid, roseoside; a sugar, lawsofructose; a coumarin, scopoletin; a diterpene, phytol; three triterpenes, pomolic acid, spinosic acid, and rotungenic acid; and five steroids, sitosterol, stigmasterol, campesterol, β-sitosterol-3-O-β-d-glucoside, and β-stigmasterol-3-O-β-d-glucoside. Some compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis and their ability to inhibit NO production by macrophages stimulated by lipopolysaccharide (LPS). The compounds pomolic acid, spinosic acid, strictosidine, and 5α-carboxystrictosidine displayed antimycobacterial activity with minimum inhibitory concentrations ranging from 7.1 to 19.2 µg/mL. These compounds showed promising inhibitory activity against NO production (IC50 3.22 to 25.5 μg/mL). 5α-carboxystrictosidine did not show cytotoxicity against macrophages RAW264.7 up to a concentration of 100 µg/mL. With the exception of strictosamide, this is the first report of the occurrence of these substances in P. nuda.

Highlights

Tuberculosis (TB) has become the communicable disease with the highest mortality rate around the world and the main cause of death among people living with HIV
The chromatographic fractionation of leaf and twig extracts of P. nuda led to the isolation of compounds: pomolic acid (1), spinosic acid (2), sitosterol (3), stigmasterol (4), campesterol (5), phytol (6), β-sitosterol-3-O-β-D-glucoside (7), β-stigmasterol-3-O-β-D-glucoside (8), cinchonain Ia (9), cinchonain Ib (10), N,N,N-trimethyltryptamine (11), lyaloside (12), lawsofructose (13), roseoside (14), strictosamide (15), scopoletin (16), rotungenic acid (17), strictosidine (18), and 5α-carboxystrictosidine
This is the first report of alkaloid (11) isolation from a natural product, as well as the isolation of the iridoid (14) and the flavonolignans (9) and (10) from the genus Psychotria

Summary

Introduction

Tuberculosis (TB) has become the communicable disease with the highest mortality rate around the world and the main cause of death among people living with HIV. The situation is further complicated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB and by HIV/AIDS coinfection [3,4]. Development of new anti-tubercular drugs is essential for curing the disease. Many diseases such as cancer, Alzheimer’s disease, and atherosclerosis, as well as infections such as TB are followed by inflammatory processes with high production of chemical mediators [5]. For protection against mycobacteria, the production of proinflammatory mediators by the infected macrophages is essential. In cases of severe forms of TB, additional anti-inflammatory therapy is required to prevent excessive inflammation [6,7]

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