A series of β-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.

O extrato etanólico das folhas de Paullinia elegans Cambess., Sapindaceae, e as frações n-hexano, clorofórmio, acetato de etila e hidroetanólica, obtidas de seu fracionamento, foram avaliadas quanto às suas atividades anti-edematogênica e sequestradora de radicais livres. O extrato etanólico e a fração hexano produziram inibição significativa (74,4 e 76,0%, respectivamente) do edema da orelha induzido pelo óleo de cróton em ratos, em doses de 5 mg/orelha. As frações acetato de etila e hidroetanólica mostraram atividade sequestradora de radicais livres no ensaio de DPPH, com IC50 de 36,7 e de 30,1 µg/mL, respectivamente. O fracionamento dos extratos pelo uso de métodos cromatográficos resultou no isolamento do epifriedelanol, ácido 3-O-acetil oleanólico, mistura do stigmasterol 3-β-O-glucopiranosídeo e sitosterol 3-β-O-glucopiranosídeo, canferol, canferol 3,7-O-α-diramnopiranosídeo, canferol 3-O-α-ramnopiranosídeo e 2-O-metil-chiro-inositol. Os compostos foram identificados com base na comparação de seus dados espectroscópicos de RMN com os da literatura.

Ethanol extract of the leaves of Paullinia elegans Cambess., Sapindaceae, and its hexane, chloroform, ethyl acetate, and hydroethanol fractions were evaluated for their antiedematogenic and free radical scavenging activities. The ethanol extract and the hexane fraction produced statistically significant inhibition (74.4 and 76.0%, respectively) of the ear edema induced by croton oil in mice, observed at doses of 5 mg/ear. The ethyl acetate and hydroethanol fractions showed significant radical scavenging effect in the DPPH assay, with IC50 of 36.7 and 30.1 µg/mL, respectively. Fractionation of the extracts through chromatographic methods afforded epifriedelanol, oleanolic acid 3-O-acetyl, a mixture of stigmasterol 3-β-O-glucopyranoside and sitosterol 3-β-O-glucopyranoside, kaempferol 3,7-O-α-dirhamnopyranoside, kaempeferol-3-O-α-rhamnopyranoside and 2-O-methyl-chiro-inositol. The compounds were identified on the basis of their NMR spectral data and comparison with those of literature.

Com o propósito de aumentar a atividade anticâncer demonstrada anteriormente pelas 1-fenilssubstituído-3-(2-tioxo-1,3,4-oxadiazol-5-il) β-carbolinas 1a-c, neste trabalho foram realizadas a síntese e a avaliação in vitro da atividade antitumoral de novas bases de Mannich 2-7(a-c), derivadas da introdução de diferentes grupos alquilamino(metil) na unidade 1,3,4-oxadiazol de 1a-c. Os derivados 1a-c e 2-7(a-c) foram também avaliados quanto às atividades antibacteriana e antifúngica. Adicionalmente, um estudo in silico das propriedades de ADME dos novos compostos sintetizados 2-7(a-c) foi realizado pela avaliação de seus parâmetros de Lipinski e de dados de área de superfície topológica polar (TPSA) e de porcentagem de absorção (% ABS).

With the purpose of activity enhancement of 1-substituted phenyl-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carbolines 1a-c, reported as potential antitumor agents in our previous study, herein we report the synthesis and antitumor activity evaluation of several novel Mannich bases 2-7(a-c), by the introduction of different alkylamino(methyl) groups in the 1,3,4-oxadiazole unity of 1a-c. The antimicrobial activities of 1a-c and of 2-7(a-c) were also evaluated. Additionally, an in silico study of the ADME properties of novel synthesized β-carboline derivatives 2-7(a-c) was performed by evaluation of their Lipinski's parameters and topological polar surface area (TPSA) and percentage of absorption (% ABS) data.