RESUMEN
The study involved the isolation and identification of a member of Streptomyces griseorubens and the identification of its secondary metabolite content. Two extract samples were prepared by using butanol and chloroform. In the analyses of the extracts TLC, FT-IR, and GC-MS were employed. Butanol extract appeared to be dominated by three different pyrrole compounds (43.59%), while two fatty acids, linoleic- and erucic acids, were the most abundant secondary metabolites in the chloroform extract, 27.57% and 12.34%, respectively. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-compound was represented by a single and distinct band on the thin layer chromatography plate. In GC-MS spectra, it also constituted 13.50% of the butanol extract.
Asunto(s)
Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Ácido Linoleico/análisis , Pirroles/análisis , Streptomyces/química , Streptomyces/metabolismo , Butanoles , Cromatografía en Capa Delgada , Ácidos Erucicos/análisis , Cromatografía de Gases y Espectrometría de Masas , Streptomyces/aislamiento & purificaciónRESUMEN
The 1,2,4-triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti-inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1-M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC50 values lower than 10 µM concentrations. The low IC 50 values of the compounds are M1 (3.88 µM), M2 (2.18 µM), M3 (4.2 µM), M4 (2.58 µM), M5 (2.88 µM), M6 (2.37 µM), M7 (3.49 µM), M8 (4.01 µM), M9 (8.90 µM), and M10 (3.12 µM).
RESUMEN
In this study, carbonic anhydrase (CA) enzyme was purified and characterized from blood samples of Kangal Akkaraman sheep and inhibitory properties on certain antibiotics were examined. CA purification was composed of preparation of the hemolysate and conducting the Sepharose-4B-tyrosine-sulfanilamide affinity gel chromatography in having specific activity of 11626 EU mg-1 , yield of 14.40%, and 242.76-fold purification. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed to assess the enzyme purity and a single band was observed. Some antibiotics were exhibited in vitro inhibition on the CA activity. IC50 values of these inhibitors were calculated by plotting activity percentage. IC50 values of certain drugs (dexamethasone; caffeine; metamizole sodium; tetramisol; ceftiofur HCl; ivermectin; tavilin 50; penokain G; neosym; and sulfamezathine) were found as 0.38, 8.24, 285.53, 114.77, 5.33, 2.76, 27.58, 213.50, 208.28, and 36.60 µM, respectively. Ki values of different drugs on Kangal Akkaraman sheep blood CA activity were found in the range of 0.21 ± 0.038-266.64 ± 37.11 µM.
Asunto(s)
Antibacterianos/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/metabolismo , Animales , Animales Endogámicos , Antibacterianos/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Unión Competitiva , Cafeína/química , Cafeína/farmacología , Inhibidores de Anhidrasa Carbónica/química , Anhidrasas Carbónicas/química , Anhidrasas Carbónicas/aislamiento & purificación , Estimulantes del Sistema Nervioso Central/química , Estimulantes del Sistema Nervioso Central/farmacología , Dexametasona/química , Dexametasona/farmacología , Eritrocitos/enzimología , Cinética , Estructura Molecular , Peso Molecular , Oveja Doméstica , TurquíaRESUMEN
Some novel derivatives of thiosemicarbazide and 1,2,4-triazole-3-thiol were synthesized and evaluated for their biological activities. The title compounds were prepared starting from readily available pyridine-2,5-dicarboxylic acid. The reaction carboxylic acid with absolute ethanol afforded the corresponding dimethyl pyridine-2,5-dicarboxylate (1). The reaction of dimethyl-2,5-pyridinedicarboxylate (1) with hydrazine hydrate good yielded pyridine-2,5-dicarbohydrazide (2). Refluxing compound 2 with alkyl/aryl isothiocyanate derivatives for 3-8 h afforded 1,4-disubstituted thiosemicarbazides (3a-e). Base-catalyzed intra-molecular dehydrative cyclization of these intermediates furnished the 4,5-disubstituted bis-mercaptotriazoles (4a-e) in good yield (85%-95%). Among the target compounds, 2,2'-(pyridine-2,5-diyldicarbonyl)bis[N-(p-methoxyphenyl)hydrazinecarbothioamide] (3c) showed very high activity with value of 72.93% against 1,1-diphenyl-2-picrylhydrazyl free radical at the concentration of 25 µg/mL. The inhibitory effects of the target compounds against acetylcholinesterase (AChE), hCA I, and II were studied. AChE, cytosolic hCA I and II isoforms were potently inhibited by synthesized these derivatives with Ki s in the range of 3.07 ± 0.76-87.26 ± 29.25 nM against AChE, in the range of 1.47 ± 0.37-10.06 ± 2.96 nM against hCA I, and in the range of 3.55 ± 0.57-7.66 ± 2.06 nM against hCA II, respectively.
Asunto(s)
Antioxidantes/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de la Colinesterasa/farmacología , Nootrópicos/farmacología , Piridinas/farmacología , Tiosemicarbazonas/farmacología , Triazoles/farmacología , Acetilcolinesterasa/química , Acetilcolinesterasa/metabolismo , Antioxidantes/síntesis química , Antioxidantes/química , Anhidrasa Carbónica I , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Anhidrasas Carbónicas/química , Anhidrasas Carbónicas/aislamiento & purificación , Anhidrasas Carbónicas/metabolismo , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Diseño de Fármacos , Humanos , Quelantes del Hierro/síntesis química , Quelantes del Hierro/química , Quelantes del Hierro/farmacología , Isoenzimas/antagonistas & inhibidores , Isoenzimas/aislamiento & purificación , Isoenzimas/metabolismo , Cinética , Estructura Molecular , Nootrópicos/síntesis química , Nootrópicos/química , Piridinas/síntesis química , Piridinas/química , Relación Estructura-Actividad , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/química , Temperatura de Transición , Triazoles/síntesis química , Triazoles/químicaRESUMEN
The aim of this study was to evaluate biologically active novel molecules having potentials to be drugs by their antitumor properties and by activities of apoptotic caspase and topoisomerase. Following syntheses of novel eight bis(α-aminoalkyl)phosphinic acid derivatives (4a-h) as a result of array of reactions, compounds were evaluated by cytotoxic effects in vitro on human breast cancer (MCF-7) and normal endothelial (HUVEC) cell lines. All phosphinic acid derivatives were effective for cytotoxicity on both MCF-7 and HUVEC lines, while 4c, 4e, and 4f compounds were found significantly more effective. For the evaluation of antitumor properties of compounds in a highly sensitive method, their effects on inhibiting topoisomerases I and II were investigated. Also, some of the bis(α-aminoalkyl)phosphinic acid derivatives (4a, 4e-h) showed nice inhibitory action against acetylcholinesterase and human carbonic anhydrase isoforms I and II.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa II/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Colinesterasa/química , ADN-Topoisomerasas de Tipo I/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células MCF-7 , Ácidos Fosfínicos/química , Inhibidores de Topoisomerasa I/química , Inhibidores de Topoisomerasa II/químicaRESUMEN
Aminophosphinic acids which are organophosphorus compounds widely investigated for potential production of antibacterial, antitumor and antiviral materials. In vitro antioxidant, cytotoxic and antimicrobial activities of synthesized novel compounds of 8 different bis(ß-amino alkyl)phosphinic acids (4a-h) were investigated on MCF-7 breast adenocarcinoma cell and human umbilical vein endothelial cell (HUVEC) cultures. Malondialdehyde (MDA) levels were evaluated as an indication of lipid peroxidation in cell cultures for antioxidant capacities. In vitro antioxidant activities in cell cultures were determined by evaluating totals of antioxidant, oxidant, thiol levels and activities of paraoxanase, aryl esterase. It was found that 4c compound reduced MDA level significantly while 4a and 4g compounds increased MDA levels significantly compared to control. 4c compound was found most effective in reducing MDA levels by neutralizing reactive oxygen species to prevent cell damage while compounds 4c, 4f and 4h were found presenting adequate activity with other antioxidants. In vitro anti-proliferation was evaluated on MCF-7 and HUVEC cells using XTT to investigate anti-cancer potentials as therapeutics. Compounds 4c, 4e and 4f were exhibited better compared to others. Most compounds were found cytotoxic to both MCF-7 and HUVECs. Antimicrobial and antifungal activities were investigated by disc diffusion and compared to MICs of Gentamycin and Nystatin.
Asunto(s)
Antioxidantes/farmacología , Proliferación Celular/efectos de los fármacos , Ácidos Fosfínicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células MCF-7 , Malondialdehído/metabolismo , Ácidos Fosfínicos/químicaRESUMEN
Ability to taste Phenylthiocarbamide (PTC) a bitter molecule, is usually used to know the heritable characteristic in both genetic and physiological studies. So far, no research has yet attested whether PTC blindness relation with obesity and some nutrition behaviors of human. This study is the first attempt on a large scale to examine PTC sensitivity in healthy and overweight people in Turkish population to define in the perception of bitter senses which is associated with nutrition habits, body mass index, age, gender, and to be in stable weight. PTC taste perception was measured by tasting PTC solution filtered in a paper. The results showed that tasters were significantly more frequent (81,8%) than nontasters (18,2%) in all population. A higher proportion of nontasters were observed in the quite fat individual group (BMI >40kg/m(2)). Alterations explained these differences in basic taste sensitivity, age, gender, BMI, individuals' family obesity situations, vegetarian nourishment. Increased frequency of nontasters allele is evident with obesity condition. This could be due to lack of preference for nutrition among nontasters. So the phenotypic variation in PTC sensitivity is genetic in origin; it may represent an association with obesity, dietary habits, regular weight, gender, and age.