ABSTRACT
In this study, we report the ring transformation of 3-arylsydnone into 1-aryl-1H-pyrazole-3-carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1-Aryl-1H-pyrazole-3-carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles which were further subjected to N-alkylation with aryl/heteroaryl alkyl halides to afford 1,5- and 2,5-disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex. Compounds 4a, 6b, 7a, 7b, 8b, and 9b showed maximum fall in the blood glucose levels in streptozotocin-induced diabetic rats after 5-7 days of administration. In support of antidiabetic activity, we also performed the experimental in vivo studies, namely, effect of compounds on enzymes (serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, creatinine, urea, and total protein), antihyperlipidemic, and histopathology. Moreover, the molecular docking study has been performed for potent molecules among the series with glycogen phosphorylase as target enzyme, and this study corroborated the experimental in vivo results.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/chemical synthesis , Glycogen Phosphorylase/antagonists & inhibitors , Tetrazoles/administration & dosage , Tetrazoles/chemical synthesis , Acrylonitrile/chemistry , Animals , Blood Glucose/drug effects , Cycloaddition Reaction , Diabetes Mellitus, Experimental/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Female , Male , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Rats , Streptozocin , Structure-Activity Relationship , Tetrazoles/chemistry , Tetrazoles/pharmacologyABSTRACT
Fused nitrogen heterocyclesnamely, pyrazolo[3,4-d]pyridazin-7(6H)-ones have been obtained by exploiting the 1,3-dipolar nature of N-arylsydnones, from hydrazones of 3-aryl-4-acetylsydnones via the Vilsmeier-Haack strategy. Facile intramolecular nucleophilic addition followed by CO2 elimination under reflux or upon microwave irradiation was presented. Plausible mechanisms for the formation of the title compounds are proffered. Structure confirmatory evidence came from single-crystal X-ray crystallography.
ABSTRACT
A simple, sensitive and reliable gas chromatography mass spectrometry (GC-MS) method has been developed, optimized and validated for the simultaneous determination of 3-chloro-1-propanol (CHP), 1,3-dichloropropane (DCP), 3-chloropropylacetate (CPA) and chloropropyl hydroxypropyl ether (CHE) contents in fudosteine, using chlorobenzene as internal standard. Efficient chromatographic separations were achieved on an Agilent J&W DB-WAXetr, 30 m long with 0.32 mm i.d., 1.0 µm particle diameter column that consists of bonded and cross-linked polyethylene glycol as a stationary phase by passing helium as the carrier gas. The analytes were extracted in dichloromethane and monitored by gas chromatography electron ionization mass spectrometry (GC-EI-MS) with selective ion monitoring (SIM) mode. The performance of the method was assessed by evaluating specificity, precision (repeatability and reproducibility), sensitivity, linearity and accuracy. The limit of detection and limit of quantification established for CHP, DCP, CPA and CHE were in the range of 0.05-0.08 µg mL(-1) and 0.10-0.17 µg mL(-1), respectively. The recoveries for CHP, DCP, CPA and CHE were in the range of 92.0-101.5%. The results proved that the method is suitable for the simultaneous determination of contents of CHP, DCP, CPA and CHE in fudosteine.
Subject(s)
Chemistry Techniques, Analytical/methods , Cystine/analogs & derivatives , Gas Chromatography-Mass Spectrometry , Mutagens/analysis , Propanols/analysis , Chemistry Techniques, Analytical/standards , Cystine/chemistry , Drug Contamination , Limit of Detection , Reproducibility of ResultsABSTRACT
A series of novel 2-(4-chlorophenyl)-5-methyl-4-(2-amine/oxy-ethyl)-2,4-dihydro-[1,2,4]triazol-3-one (5a-t) were synthesized and in vitro anticancerous action of the resulting compounds was studied against NCI-60 Human Tumor Cell Line at a single high dose (10(-5) M) concentration for primary cytotoxicity assay. Among the tested compounds (5a-e, 5g-h, 5k, 5p), the compound 5g (NSC: 761736/1) was further evaluated for five dose criteria at five different minimal concentrations against the full panel of 60 human tumor cell lines which exhibited activity against Leukemia (GI50: 1.10 µM), Non-Small Cell Lung Cancer (GI50: 1.00 µM), Renal Cancer (GI50: 1.00 µM), Colon Cancer (GI50: 1.66 µM), CNS Cancer (GI50: 1.36 µM), Melanoma (GI50: 1.82 µM), Ovarian Cancer (GI50: 1.64 µM) and Breast Cancer (GI50: 1.69 µM).
Subject(s)
Antineoplastic Agents/pharmacology , Coumarins/pharmacology , Triazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
Novel tricyclic carbazoles 4a-k were synthesized in one-pot employing sydnone derivatives 3a-k as masked hydrazines by the ring transformation in presence of conc. HCl and cyclohexanone. The title compounds were screened for anti-tubercular, anti cancer, DNA cleavage, antioxidant activity. MIC, GI50, LC50, TGI were evaluated. The title compounds have exhibited significant antitubercular, DNA cleavage and antioxidant activities and partial anticancer activity.
