Planta Med
DOI: 10.1055/a-1157-1732
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antimycobacterial Activity of Alkaloids and Extracts from Tabernaemontana alba and T. arborea

Silvia Laura Guzmán-Gutiérrez
1  CONACyT – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Mayra Silva-Miranda
1  CONACyT – Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Felix Krengel
2  Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, México
3  Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Elizabeth Huerta-Salazar
3  Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Mayra León-Santiago
3  Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Jessica Karina Díaz-Cantón
2  Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, México
3  Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Clara Espitia Pinzón
4  Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
,
Ricardo Reyes-Chilpa
3  Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, México
› Author Affiliations
Supported by: Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica PAPIIT, Universidad Nacional Autónoma de México. IG200418
Supported by: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México
Further Information

Publication History

received 09 January 2020
revised 19 March 2020

accepted 13 April 2020

Publication Date:
11 May 2020 (online)

Abstract

Tuberculosis is the main cause of death from a single infectious agent. Globally, according to the World Health Organization, in 2018, there were an estimated 1.2 million tuberculosis deaths. Moreover, there is a continuous appearance of drug-resistant strains. Thus, development of new antituberculosis medicines should receive high priority. Plant-derived natural products are promising candidates for this purpose. We therefore screened alkaloid extracts obtained from the root and stem barks of the Mexican Apocynaceae species Tabernaemontana alba and Tabernaemontana arborea, as well as the pure alkaloids ibogaine, voacangine, and voacamine, tested for activity against Mycobacterium tuberculosis H37Rv and cytotoxicity to mammalian Vero cells using the resazurin microtiter and the MTT assays, respectively. The extracts were analyzed by GC-MS and HPLC-UV. T. arborea root bark alkaloid extract showed the highest activity against M. tuberculosis (MIC100 = 7.8 µg/mL) of the four extracts tested. HPLC suggested that voacangine and voacamine were the major components. The latter was isolated by column chromatography, and its chemical structure was elucidated by 1H and 13C NMR, and MS. Unambiguous assignation was performed by HSQC, HMBC, and NOESY experiments. Voacamine is a dimeric bis-indole-type alkaloid and is 15 times more potent than the monomeric ibogan-type alkaloids ibogaine and voacangine (MIC100 = 15.6, 250.0, and 250.0 µg/mL, respectively). However, all of these compounds showed cytotoxicity to Vero cells, with a poor selectivity index of 1.00, 0.16, and 1.42, respectively. This is the first report of voacamine activity against M. tuberculosis.

Supporting Information