Artículos de revistas
Synthesis, In Vitro Antiproliferative And Anti-mycobacterium Tuberculosis Activities Of Novel Beta-carboline Derivatives
Registro en:
Journal Of The Brazilian Chemical Society. Soc Brasileira Quimica, v. 27, p. 1398 - 1405, 2016.
0103-5053
1678-4790
WOS:000383789500008
10.5935/0103-5053.20160062
Autor
Moreira
Flora M. F.; Croda
Julio; Sarragiotto
Maria H.; Foglio
Mary A.; Ruiz
Ana L. T. G.; Carvalho
Joao E.; Formagio
Anelise S. N.
Institución
Resumen
A series of beta-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) beta-carboline (24.9 mu g mL(-1)) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) beta-carboline (26.9 mu g mL(-1)) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide( ethylamine) beta-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) beta-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI(50)) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) beta-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) beta-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3carboxamide(ethyl) guanidine beta-carboline (27.8 mu g mL(-1)) and 1-(3-nitrophenyl)-3-carboxamide(ethyl) guanidine beta-carboline (37.4 mu g mL(-1)) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl) guanidine beta-carboline (GI(50) = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) beta-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) beta-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) beta-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) beta-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) beta-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability. 27 8 1398 1405