RESUMO
Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques. Most of the tested compounds showed more promising inhibition potential than the standard acarbose (IC50 = 14.87 ± 0.16 µM) but compounds 13 and 12 were found to be the most potent compounds with IC50 values of 9.20 ± 0.14 µM and 3.05 ± 0.18 µM against α-amylase and α-glucosidase enzymes, respectively. Compounds 1-34 also displayed moderate antioxidant potential in the range of IC50 = 96.50 ± 0.45 to 189.98 ± 1.00 µM in comparison to the control butylated hydroxytoluene (BHT) (IC50 = 66.50 ± 0.36 µM), in DPPH radical scavenging activities. Additionally, all synthetic derivatives were subjected to a molecular docking study to investigate the interaction details of compounds 1-34 (ligands) with the active site of enzymes (receptors). These results indicate that the newly synthesized pyridone class may serve as promising lead candidates for controlling diabetes mellitus and as antioxidants.
Assuntos
Antioxidantes , alfa-Glucosidases , Antioxidantes/farmacologia , Antioxidantes/química , alfa-Glucosidases/metabolismo , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , alfa-Amilases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/químicaRESUMO
During the past few decades the emergence of inorganic medicinal chemistry has been developed novel therapeutic agents. Researcher's perseverance in this branch of chemistry has led them to explore further valuable chemical spaces by synthesizing metal complexes already known pharmacological agents for their potential use. However, it is in its early stage, this methodology has demonstrated metal complexes with better bioactivities than the parent ligand molecules. In this study, transition metal complexes of pyrazinamide (PZ), isoniazid (INH), fluconazole (FCZ), metformin (dimethylbiguanide, DMBG) and losartan potassium (LS-K) were selected to evaluate for their possible anti-platelets aggregation in the light of reports on divalent and trivalent cations like calcium, copper, manganese, magnesium, and cadmium may influence the process of thrombocytic activity and aggregation. The required evaluation was carried out on human plasma through an APACT 4004 platelet aggregation analyzer. Arachidonic acid (ADP) was used to gauge any alteration in platelet shape and aggregation process. The parent drugs showed some anti-platelets aggregation, however, their metal complexes demonstrated better efficacy.
Assuntos
Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Fluconazol/química , Humanos , Isoniazida/química , Losartan/química , Metformina/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Pirazinamida/químicaRESUMO
Use of drug-metal complexes for the treatment of several human diseases has resulted in significant progress in the field of medicinal inorganic chemistry. The current study describes the synthesis and characterization of Cu (II) and Ni (II) complexes of Losartan, an antihypertensive drug. These complexes were evaluated for their cytotoxic activity against four human cancer cell lines; SNB-19, HCT-15, COLO-205 and KB-3-1. Spectroscopic characterization revealed that during complex formation, the metal was bound through the nitrogen atoms of the tetrazole moiety of the losartan molecule. The molecular formulas of copper ([Cu (LS) 2 Cl2].6H2O) and nickel ([Ni (LS) 2Cl2]. H2O) complexes were found to be in agreement with the analytical data obtained through elemental analysis. For both the complexes, metal to ligand ratios of 1:2 were calculated. As revealed by FTIR, UV-Visible, and 1H-NMR studies, both the complexes displayed octahedral geometries. Scanning electron microscopy (SEM) revealed marked changes in the morphology of the complexes, compared to the pure drug. From XRD studies, characteristic crystalline peaks of pure losartan were observed whereas no prominent peaks were observed for its complexes. Complexes were found to be inactive in the cytotoxic activity test performed using SNB-19, HCT-15, COLO-205 and KB-3-1 cell lines.
Assuntos
Antiarrítmicos/análise , Complexos de Coordenação/análise , Citotoxinas/análise , Losartan/análise , Espectroscopia de Ressonância Magnética/métodos , Antiarrítmicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Complexos de Coordenação/toxicidade , Citotoxinas/toxicidade , Humanos , Losartan/toxicidadeRESUMO
The human digestive tract contains some 100 trillion cells and thousands of species of micro-organisms may be present as normal flora of this tract as well as other mucocutaneous junctions of the body. Candida specie is the most common organism residing in these areas and can easily invade the internal tissues in cases of loss of host defenses. Modifications of previously existing antifungal agents may provide new options to fight against these species. Inorganic compounds of different antifungals are under investigations. Present study report six complexes of fluconazole with Cu (II)), Fe(II), Cd(II), Co(II), Ni(II) and Mn(II) have been synthesized and characterized by elemental analysis, IR, UV and H-NMR. The elemental analysis and spectroscopic data were found in agreement with the expected values as the metal to ligand value was 1:2 ratios with two chlorides in coordination sphere. The morphology of each complex was studied using scanning electron microscope and compared with fluconazole molecule the flaky-slab rock like particles of pure fluconazole was also observed as reported earlier. However, the complexes of fluconazole were showed different morphology in their micrograph. Fluconazole and its complex derivatives have also been screened in vitro for their antifungal activity against Candida albican and Aspergillus niger by MIC method. The complexes showed varied activity ranging from 2-20%.
Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Fluconazol/química , Fluconazol/farmacologia , Metais Pesados/química , Microscopia Eletrônica de Varredura , Tecnologia Farmacêutica/métodos , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cloretos/química , Cloretos/farmacologia , Fluconazol/análogos & derivados , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de SuperfícieRESUMO
The synthetic indole Mannich bases 1-13 have been investigated for their ability to modulate immune responses measured in vitro. These activities were based on monitoring their affects on T-lymphocyte proliferation, reactive oxygen species (ROS), IL (interleukin)-2, IL-4, and nitric oxide production. Compound 5 was found to be the most potent immunomodulator in this context. Four of the synthesized compounds, 5, 11, 12, and 13, have significant potent inhibitory effects on T-cell proliferation, IL-4, and nitric oxide production. However, none of the thirteen indole compounds exerted any activity against ROS production.
Assuntos
Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Indóis/química , Indóis/farmacologia , Bases de Mannich/química , Bases de Mannich/farmacologia , Adulto , Animais , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Humanos , Óxido Nítrico/imunologia , Espécies Reativas de Oxigênio/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
The title mol-ecule, C10H10N4O2, is almost planar and adopts an E configuration of the azomethine [C=N = 1.298â (2)â Å] double bond. The benzene ring is attached to an essentially planar (r.m.s. deviation = 0.0226â Å) amidine moiety (N=CN/Me2), the dihedral angle between the two mean planes being 18.42â (11)°. The cyano group lies in the plane of the benzene ring [the C and N atoms deviating by 0.030â (3) and 0.040â (3)â Å, respectively], while the nitro group makes a dihedral angle 5.8â (3)° with the benzene ring. There are two distinct inter-molecular hydrogen bonds, C-Hâ¯O and C-Hâ¯N, that stabilize the crystal structure; the former inter-actions result in centrosymmetric dimers about inversion centers resulting in ten-membered rings, while the later give rise to chains of mol-ecules running parallel to the b axis.
RESUMO
We report thermal, X-ray diffraction (XRD) and cytotoxicity studies of complexes of fluconazole (FCZ) with Cu (II), Fe(II), Cd(II), Co(II), Ni(II), and Mn(II). From XRD measurements, FCZ and its metal complexes were identified as polycrystalline. Marked differences in the X-ray patterns of drug and its metal complexes revealed that the complexes are indeed different compounds and not just the mixture of the starting materials. Unlike pristine FCZ, which did not exhibit cytotoxicity, three complexes derived from Fe(II), Cu(II) and Co (II) proved to be effective in the cytotoxicity assay. The Cu(II)-FCZ exhibited significant activity against SNB-19, HCT-15, COLO-205, and KB-3-1 cell lines, while Fe(II)-FCZ and Co(II)-FCZ were found cytotoxic only to KB-3-1 cell line. For the pure FCZ, thermogravimetry revealed massive weight loss in the temperature range of 215 to 297 °C, due to the volatilization of FCZ. All the complexes followed multi-stage degradation profiles, eventually resulting in the formation of metal oxides. For pure FCZ, differential scanning calorimetry revealed melting point at 137 °C, followed by two further endothermic transitions at 294 °C and 498.44 °C representing the volatilization and subsequent degradation of FCZ, respectively. The absence of endothermic FCZ melting peak at around 137 °C indicates that the complexes represent different compounds. All complexes exhibit endothermic transitions at around 240-300 °C, representing melting and removal of ligand moiety, followed by another endothermic transition at around 498-499 °C, representing the ligand decomposition.
RESUMO
Three glycosides and a long chain alcohol were isolated from the bulbs of Polianthes tuberosa, these were identified as 3,29-dihydroxystigmast-5-ene-3-O-beta-D-galactopyranoside (1), ethyl beta-D-galactopyranoside (2), ethyl-alpha-D-galactopyranoside (3), and 1-tricosanol (4). The structures were determined by extensive spectroscopic and chemical methods. All four isolated compounds were screened for their cytotoxicity, antibacterial and antifungal activities, none of the compounds showed any significant activity.