RESUMEN
The chemical investigation of Chromolaena palmaris (Sch.Bip. ex Baker) R.M. King & H. Rob. expands the phytochemical composition knowledge of Chromolaena genus, since this is the first chemical investigation of this species. Twenty-five compounds were identified, including a phytoprostane, 17 flavonoids, 6 phenolic acids, and a caffeoyl-glucoside derivative obtained by classical chromatography and UHPLC-HRMS/MS analysis. Moreover, anti-Mycobacterium tuberculosis and antiproliferative activities of C. palmaris were evaluated. Dichloromethane fraction showed cytotoxicity towards human cancer cell lines, presenting TGI values on glioma (U251) of 27.8 µg mL-1. Furthermore, compounds 1 and 2 exhibited antimicrobial activity against Mycobacterium tuberculosis with MIC of 62.5 and 15.6 µg mL-1, respectively.
Asunto(s)
Antiinfecciosos , Chromolaena , Tuberculosis , Antiinfecciosos/farmacología , Chromolaena/química , Flavonoides/química , Glucósidos , Humanos , Cloruro de Metileno , Fenoles/farmacología , Fitoquímicos , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
A total of forty-three compounds were synthesized, including thirty-two new ones. Among those compounds, seventeen were selected and tested on human tumor cell lines: PC-3 (prostate adenocarcinoma), HCT-116 (colorectal tumor), NCIH-460 (lung carcinoma), SKMEL-103 (melanoma) and AGP-01 (gastric tumor). Alkynylated 1,2,4-oxadiazoles 2m, 3g and 3k exhibited antiproliferative activities against NCIH-460 in culture. Alkynylated N-cyclohexyl-1,2,4-oxadiazoles 3a-m and bis-heterocycle glucoglycero-1,2,3-triazole-N-cyclohexyl-1,2,4-oxadiazole derivatives 5a-k and 6-11 were evaluated for their in vitro efficacy towards Mycobacterium tuberculosis (Mtb) H37Ra and H37Rv strains. In general, glycerosugars conjugated to 1,2,4-oxadiazole via a 1,2,3-triazole linkage (5a, 5e, 5j, 5k, and 7) showed in vitro inhibitory activity against Mtb (H37Rv). The largest molecules bis-triazoles 10 and 11, proved inactive against TB. Probably, the absence of the N-cyclohexyl group in compound 8 and 1,2,4-oxadiazole nucleus in compound 9 were responsible for its low activity. Glucoglycero-triazole-oxadiazole derivatives 5e (10 µM) and 7 (23.9 µM) were the most promising antitubercular compounds, showing a better selective index than when tested against RAW 264.7 and HepG2 cells. Vero cell were used to investigate cytotoxicity of compounds 5a, 5h, 5j, 5k, and these compounds showed good cell viability. Further, in silico studies were performed for most active compounds (5e and 7) with potential drug targets, DprE1 and InhA of Mtb to understand possible interactions aided with molecular dynamic simulation (100ns).
Asunto(s)
Antineoplásicos/farmacología , Antituberculosos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Glicoconjugados/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Mycobacterium tuberculosis/efectos de los fármacos , Oxadiazoles/química , Alquinos/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antituberculosos/síntesis química , Antituberculosos/química , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Glicoconjugados/síntesis química , Glicoconjugados/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Triazoles/químicaRESUMEN
The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.
Asunto(s)
Antineoplásicos/farmacología , Antituberculosos/farmacología , Serina/análogos & derivados , Serina/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antituberculosos/síntesis química , Antituberculosos/química , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Serina/síntesis química , Serina/química , Células VeroRESUMEN
ABSTRACT A new C-glycosylflavone, apigenin 7-methyl ether 6-C-[β-xylopyranosyl-(1→3)-β-glucopyranoside] named distemonanthoside was isolated from the stem bark of Distemonanthus benthamianus Baill., Fabaceae, along with six known compounds, sitosterol 3-O-β-D-glucopyranoside, 4-methoxygallic acid, syringic acid, quercetin, 6"-O-acetylvitexin, quercetin 3-O-β-D-glucopyranoside. The structures of those compounds and others were determined through spectral analyses. Compounds distemonanthoside, sitosterol 3-O-β-D-glucopyranoside, 4-methoxygallic acid and quercetin were tested against a clinical isolate strain of Mycobacterium tuberculosis AC 45; they exhibited good to moderate antitubercular activities with MIC values ranged from 31.25 to 125 µg/ml.
RESUMEN
Novel gold(I) and gold(III) complexes containing derivatives of D-galactose, D-ribose and D-glucono-1,5-lactone as ligands were synthesized and characterized by IR, (1)H, and (13)C NMR, high resolution mass spectra and cyclic voltammetry. The compounds were evaluated in vitro for their cytotoxicity against three types of tumor cells: cervical carcinoma (HeLa) breast adenocarcinoma (MCF-7) and glioblastoma (MO59J) and one non-tumor cell line: human lung fibroblasts (GM07492A). Their antitubercular activity was evaluated as well expressed as the minimum inhibitory concentration (MIC90) in µg/mL. In general, the gold(I) complexes were more active than gold(III) complexes, for example, the gold(I) complex (1) was about 8.8 times and 7.6 times more cytotoxic than gold(III) complex (8) in MO59J and MCF-7 cells, respectively. Ribose and alkyl phosphine derivative complexes were more active than galactose and aryl phosphine complexes. The presence of a thiazolidine ring did not improve the cytotoxicity. The study of the cytotoxic activity revealed effective antitumor activities for the gold(I) complexes, being more active than cisplatin in all the tested tumor cell lines. Gold(I) compounds (1), (2), (3), (4) and (6) exhibited relevant antitubercular activity even when compared with first line drugs such as rifampicin.
Asunto(s)
Carbohidratos/química , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/química , Oro/química , Carbohidratos/administración & dosificación , Carbohidratos/síntesis química , Cisplatino/administración & dosificación , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Oro/administración & dosificación , Células HeLa , Humanos , Ligandos , Pulmón/efectos de los fármacos , Pulmón/patología , Células MCF-7 , Espectroscopía de Resonancia Magnética , Rifampin/administración & dosificación , Relación Estructura-ActividadRESUMEN
O objetivo deste trabalho foi realizar uma seleção de algumas plantas de uma determinada região Brasileira com atividade contra Mycobacterium tuberculosis. Extratos clorofórmicos e metanólicos de 37 espécies de plantas distribuídas em 17 famílias do "Cerrado" Brasileiro foram avaliadas contra M. tuberculosis H37Rv e a Concentração Inibitória Mínima (CIM) foi determinada pelo uso do Microplate Alamar Blue Assay (MABA). Extratos brutos de dezesseis plantas apresentaram valor de CIM < 125 µg/mL e três de 31,2 µg/mL. Estes resultados sugerem que o "Cerrado" Brasileiro deve possuir um recurso de plantas com constituintes ativos anti-M. tuberculosis que podem ser extraídos por solventes polares e apolares.
The aim of this work was to carry out a screening of some plants of this Brazilian region with activity against Mycobacterium tuberculosis. Chloroform and methanol extracts of 37 plant species distributed among 17 families from Brazilian "Cerrado" which were tested against M. tuberculosis H37Rv and the Minimum Inhibitory Concentration (MIC) was determined by the use of Microplate Alamar Blue Assay (MABA). Crude extracts from sixteen plants showed MIC value of < 125 µg/mL and three 31.2 µg/mL. These results suggest that the Brazilian "Cerrado" may be a source of plants that have activity anti-M. tuberculosis constituents that can be extracted by polars and apolars solvents.