Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

Diversos derivados benzilideno/furfurilideno piridazin(2H)-3-ona 6-aril-4-substituídos (4a-f) foram sintetizados e avaliados como analgésicos e anti-inflamatórios em camundongos e ratos, respectivamente. Todos os compostos foram testados utilizando-se o método de placa quente de Eddy e o de edema de pata induzido por carragenana para a avaliação das atividades analgésica e anti-inflamatória, respectivamente. Os resultados mostraram que os compostos 4f, 4b, 4d e 4e exibiram atividade analgésica e anti-inflamatória mais alta do que os compostos restantes. Todos os compostos (4a-f) foram caracterizados por IV, RMN e espectrometria de massas.Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy

Molecular docking study to elucidate the anti-pruritic mechanism of selected natural ligands by desensitizing TRPV3 ion channel in Psoriasis: An in silico approach

578-583Psoriasis is a chronic immune-mediated inflammatory skin disease, in which pruritus is a common feature and also affects the social well-being of individuals with psoriasis significantly. The transient receptor potential cation channel, subfamily V, member 3 (TRPV3) is believed to be involved in hypersensation and generation of itching in the case of psoriasis. The purpose of the present study was to find out suitable anti-pruritic agents and to establish the mechanism of actions of those anti-pruritic agents with the help of molecular docking studies, through which they can alleviate the itching and hypersensitivity problems in psoriasis. An extensive literature survey, pertaining to natural ligands having reported antipsoriatic activity was carried out. The crystal structure of the TRPV3 receptor was retrieved from rcsb.org. 3D structures of selected eleven natural ligands were prepared and optimized by ChemSketch free version 2015. Computational protein- ligand docking studies were carried out by AutoDock 4.2 simulator using the Lamarckian genetic algorithm. In this study, Hypericin showed a higher binding affinity (-8.09 kcal/mol) and fitted into the active pocket of TRPV3. Results revealed that Hypericin might be the candidates to be employed as an anti-pruritic agent in the case of psoriasis to desensitize the TRPV3 ion channel

A bioinformatic approach to establish P38α MAPK inhibitory mechanism of selected natural products in psoriasis

165-171In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38α mitogen-activated protein kinases (P38α MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38α MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38α MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (−9.00 and −8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action

Morphoanatomy and phytochemical screening of entire fruits of Momordica tuberosa Cogn. (Cucurbitaceae)

Momordica tuberosa (Cucurbitaceae) is traditionally used as abortifacient in India. Morphoanatomy, physicochemical and phytochemical nature of fruits and seeds of this plant were studied in order to contribute to complete the profile of these parts to aid in their identification and avoid confusion in taxanomic species. Macroscopic and microscopic characters were established using light microscopy, WHO recommendations and standard physicochemical and phytochemical procedures. Fruits presented the typical characters of Cucurbitaceae plants possessing ridges with 1 mm thickness and pericarp 550 µm thick. Phytochemical screening revealed the presence of flavonoids, steroids, triterpenes and alkaloids in various extracts. The findings from morphoanatomy, microscopy and physicochemical characters may be used to establish the authenticity of fruits of this plant.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy

In-vivo Anticonvulsant and In-vitro Antitubercular Activity of methyl Indole Derivative of some 6-aryl-4, 5-Dihydropyridazin-3(2H)-ones and their Expected Anticonvulsant Mechanisms: Anticonvulsant & Anti-TB activity of 6-aryl-dropyridazin-3(2H)-nes

Methyl indole derivative of some 6-aryl-4,5-dihydropyridazin-3(2H)-ones (3a-e) were synthesized by Mannich reaction and evaluated as anticonvulsant against MES (50mA, for 2sec), INH (250mg/kg), scPTZ (80mg/kg) and STR (3mg/kg) induced convulsion methods at 50 mg/kg dose level. All compounds 3a-e were also evaluated as antitubercular agent against M. tuberculosis H37Rv by MABA method. All compounds 3a-e showed anticonvulsant activities against MES, INH and scPTZ-induced convulsions methods but no compounds were active against STR-induced method. Compound 3b, compound 3d and 3e showed highest protection against MES, INH and scPTZ-induced convulsion models respectively. Compound 3d showed highest antitubercular activity, with 12.5μg/ml MIC value. Previous data reported that the pyridazinones are the important biological compounds which possess almost all types of biological activities. Due to this reason, we synthesized some pyridazinone compounds and characterized them by spectral analysis. Results indicated that title compounds showed moderate to good anticonvulsant activities but less antitubercular activity

A bioinformatic approach to establish P38α MAPK inhibitory mechanism of selected natural products in psoriasis

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38α mitogen-activated protein kinases (P38α MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38α MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38α MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (−9.00 and −8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action

Antioxidant and hepatoprotective activity of tubers of <i style="">Momordica tuberosa</i> Cogn. against CCl₄ induced liver injury in rats

510-513Hydro alcoholic extract of tubers of M. tuberosa was subjected to preliminary phytochemical screening and evaluated for in vitro and in vivo antioxidant and hepatoprotective activity against CCl4 induced liver damage in rats. Pretreatment with 70% ethanolic extract of M. tuberosa reversed CCl4 induced elevation of levels of serum biomarkers to near normal levels, suggesting that the tubers of M. tuberosa possess hepatoprotective property and this property may be attributed to the antioxidant property of the plant

Pharmacognostical studies on tubers of Momordica tuberosa Cogn., Cucurbitaceae

The study was aimed at establishing pharmacognostical profile for the tubers of plant Momordica tuberosa Cogn., Cucurbitaceae. Morphoanatomy of tubers of this plant were studied in order to establish its complete profile to aid in its identification and avoid confusion in its taxanomic species. These were established using light microscopy, WHO recommended physicochemical and phytochemical procedures. The parameters presented here may be used to establish the authenticity of tubers of this plant as this part has been used traditionally in India and also to differentiate between closely related Momordica species