New Isoflavonoids from the extract of Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC. and their antimycobacterial activity
Por:
Wenceslao Coronado-Aceves, Enrique, Gigliarelli, Giulia, Garibay-Escobar, Adriana, Robles Zepeda, Ramon Enrique, Curini, Massimo, Lopez Cervantes, Jaime, Ines Espitia-Pinzon, Clara Ines, Superchi, Stefano, Vergura, Stefania, Marcotullio, Maria Carla
Publicada:
12 jul 2017
Resumen:
Ethnopharmacology relevance: The evaluation of the antimycobacterial
activity of extracts of medicinal plants used by Mayos against
tuberculosis and respiratory problems, allowed the identification of
Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC (Fabaceae) as the
best candidate to find new antimycobacterial compounds.
Aim of the study: To isolate and characterize the compounds of R.
precatoria responsible for the inhibitory and bactericidal activity
against Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis
ATCC 700084. To determine antimycobacterial synergistic effect of pure
compounds and their selectivity index towards Vero cells.
Materials and methods: A total of six flavonoids were purified by silica
gel column chromatography. Structural elucidation of the isolated
compounds was achieved by using 1D and 2D NMR spectroscopy techniques.
The configuration at the C-3 chiral center was established by quantum
mechanical calculation of the electronic circular dichroism (ECD)
spectrum. In vitro inhibitory and bactericidal activity against M.
tuberculosis and M. smegmatis were determined with the redox indicator
Alamar Blue (resazurin). Synergy was determined by X/Y quotient.
Cytotoxicity was measured by MTT assay.
Results: The isolated compounds were identified as precatorin A (1),
precatorin B (2), precatorin C (3), lupinifolin (4), cajanone (5) and
lupinifolinol (6). Compounds 1-3 are new. Compounds 1 to 5 inhibited the
growth of M. tuberculosis (MIC >= 31.25 mu g/mL); compounds 1, 2, 4 and
5 killed the bacteria (MBC >= 31.25 mu g/mL) and also inhibited M.
smegmatis (MIC >= 125 mu g/mL), while 1 and 4 also resulted bactericidal
(MBC >= 125 mu g/mL). Compounds 4 and 5 presented synergistic effect
(X/Y quotient value < 0.5) at a concentration of 1/2 MIC of each
compound in the combination. Cytotoxicity in murine macrophages (RAW
264.7 cells) gave IC50 values of 13.3-46.98 mu M, for compounds 1-5.
Conclusions: In this work we isolated two new isoflavanones (1 and 2),
and one new isoflavone (3) with a weak antimycobacterial activity. The
(3R) absolute configuration was assigned to 1 by computational analysis
of its ECD spectrum and to 2 and 5 by similarity of their ECD spectra
with that of 1. We are also reporting by first time, activity against
virulent strain of M. tuberculosis for compounds 4 and 5 and their
antimycobacterial synergistic effect.
Filiaciones:
Wenceslao Coronado-Aceves, Enrique:
Univ Sonora, Dept Chem Biol, Blvd Luis Encinas & Rosales S-N, Hermosillo 83000, Sonora, Mexico
Technol Inst Sonora, Dept Biotechnol & Alimentary Sci, 5 Febrero 818 Sur, Obregon 85000, Sonora, Mexico
Gigliarelli, Giulia:
Univ Perugia, Dept Pharmaceut Sci, Via Liceo 1, I-06123 Perugia, Italy
Garibay-Escobar, Adriana:
Univ Sonora, Dept Chem Biol, Blvd Luis Encinas & Rosales S-N, Hermosillo 83000, Sonora, Mexico
Robles Zepeda, Ramon Enrique:
Univ Sonora, Dept Chem Biol, Blvd Luis Encinas & Rosales S-N, Hermosillo 83000, Sonora, Mexico
Curini, Massimo:
Univ Perugia, Dept Pharmaceut Sci, Via Liceo 1, I-06123 Perugia, Italy
Lopez Cervantes, Jaime:
Technol Inst Sonora, Dept Biotechnol & Alimentary Sci, 5 Febrero 818 Sur, Obregon 85000, Sonora, Mexico
Ines Espitia-Pinzon, Clara Ines:
Univ Nacl Autonoma Mexico, Biomed Res Inst, Immunol Dept, Mexico City 04510, DF, Mexico
Superchi, Stefano:
Univ Basilicata, Dept Sci, Via Ateneo Lucano 10, I-85100 Potenza, Italy
Vergura, Stefania:
Univ Basilicata, Dept Sci, Via Ateneo Lucano 10, I-85100 Potenza, Italy
Marcotullio, Maria Carla:
Univ Perugia, Dept Pharmaceut Sci, Via Liceo 1, I-06123 Perugia, Italy
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