Artículos de revistas
Synthesis, In Vitro Antiproliferative And Anti-mycobacterium Tuberculosis Activities Of Novel Carboline Derivatives
Registro en:
Journal Of The Brazilian Chemical Society. Sociedade Brasileira De Química, v. 27, n. 8, p. 1398 - 1405
0103-5053
S0103-50532016000801398
Autor
Moreira
Flora M. F.; Croda
Julio; Sarragiotto
Maria H.; Foglio
Mary A.; Ruiz
Ana L. T. G.; Carvalho
João E.; Formagio
Anelise S. N.
Institución
Resumen
A series of 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) β-carboline (24.9 µg mL-1) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline (26.9 µg mL-1) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI50) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (27.8 µg mL-1) and 1-(3-nitrophenyl)-3-carboxamide(ethyl)guanidine β-carboline (37.4 µg mL-1) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (GI50 = 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) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability. 27 8 1398 1405