Synthesis and evaluation of analgesic, anti-asthmatic activity of (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 ones

Abstract Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2 , 4 , 12 , 14 , and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy's hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2 , 4 , 7 , 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2 , 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents

Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle

Starvation Sensing by Mycobacterial RelA/SpoT Homologue Through Constitutive Surveillance of Translation

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in a translation initiation complex reveals unknown interactions between the ACT domain of Rsh and components of the ribosomal L7/L12 stalk base, suggesting that the aminoacylation status of A-site tRNA is surveilled during the first cycle of elongation. Altogether, we propose a surveillance model of Rsh activation that originates from its constitutive interaction with the ribosomes entering the translation cycle

Delays in Diagnosis of Pulmonary Lymphangitic Carcinomatosis due to Benign Presentation

The diagnosis of lymphangitic carcinomatosis is challenging due to the manifestation of nonspecific symptoms and radiographic abnormalities that bear similarity to those of interstitial lung disease. Herein, we report the case of a 53-year-old woman diagnosed with lymphangitic carcinomatosis from metastatic gastric adenocarcinoma, 3 months after her initial presentation

Assessment Of Physico-Chemical Factor In Ghaggar River With Special References Of Hanumangarhregion.

This study aimed to investigate the physico-chemical parameters of the water in the Ghaggarriver, specifically at the sample location in the Hanumangarh area. Hanumangarh is located on the banks of the Ghaggar River, in the northern region of Rajasthan. Samples were taken for the purpose of investigating a range of physico-chemical parameters, including temperature, pH, total hardness, total alkalinity, salinity, turbidity, chlorides, and dissolved oxygen (DO). The  water  quality  of Ghagger are  not suitable  for  the  survival  of  fish,  aquatic life  and  migratory birds due to higher concentration of pH and lower concentration of dissolved oxygen

Facile synthesis of alkoxyphthalimide derivatized benzimidazole assembled pyrazoles, pyrimidines and isoxazoles, via common intermediate chalcone

1096-1107In the present investigation, synthesis of 2-(3-aryl-2-phenyl-3,4-dihydropyrazol-5-yl)-1-N-alkoxyphthalimidobenzimidazole 9a-h, 4-(1-N-alkoxyphthalimidobenzimidazol-2-yl)-6-arylpyrimidin-2-amine 10a-h and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)-1-N-alkoxyphthalimidobenzimidazole 11a-h are described. Mild dichromate oxidation of 1-benzimidazol-2-yl-ethanol 1 gives 1-benzimidazol-2-yl-ethanone 2 which on Clasien condensation with various aromatic aldehydes yields the corresponding 3-aryl-1-(benzimidazol-2-yl)-prop-2-en-1-one 3a-d derivatives. Compound 3a-d act as key intermediates for all the three series of final compounds. In one pathway 3a-d is converted to its alkoxyphthalimide derivatives 5a-h by condensation with ω-bromoalkoxyphthalimides 4a-b, which cyclize with PhNHNH2/pyridine, guanidine nitrate/10% NaOH and hydroxylamine hydrochloride/CH₃COOH to give 9a-h, 10a-h and 11a-h respectively. In an alternative route, reaction of 3a-d with all the three reagents affords 2-(3-aryl-2-phenyl-3,4-dihydropyrazol-5-yl)benzimidazole 6a-d, 4-(benzimidazol-2-yl)-6-arylpyrimidin-2-amine 7a-d and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)benzimidazole 8a-d which on condensation with ω-bromoalkoxyphthalimides 4a-b give the final compounds 9a-h, 10a-h and 11a-h. Structure elucidations of all the compounds have been accomplished by elemental analysis, IR, ¹H NMR and mass spectral data

Synthesis and characterization of some alkoxyphthalimide derivatives of benzotriazolylthiadiazoles and benzotriazolylthiazolidinones

860-865In the present investigation newer and simple synthetic methods of 5-(1,2,3-benzotriazol-1-yl-methyl)-N-alkoxyphthalimido-1,3,4-thiadiazol-2-amines 5a-b and 2-[(1,2,3-benzotriazolyl)acetohydrazido]-3-N-alkoxyphthalimido-5-arylidene-1,3-thiazolidin-4-ones 9a-h are described. Benzotriazole 1 is converted to carbothioamide 3 by the reaction with ethylchloroacetate followed by thiosemicarbazide. Compound 3 has acted as key intermediate for both series of the final compounds. In one pathway, 3 is converted to corresponding thiadiazole 4 by treatment with Conc. H₂SO₄ and NH₃, which on condensation with ω-bromoalkoxyphthalimide 10a-b gives 5a-b. In an alternative route reaction of 3 with chloroacetic acid and aromatic aldehydes 7a-d has afforded the formation of 2-[(1,2,3-benzotriazolyl)acetohydrazido]-5-arylidene-1,3-thiazolidin-4-ones 8a-d, which are further treated with 10a-b to furnish the final compounds 9a-h. Structural elucidation is accomplished by IR, ¹H NMR and mass spectral data of the synthesized compounds

Synthesis and Antibiotic Activity of Mebendazole Derivatives of Pharmacological Interest

Mebendazole is a well known anti-helimintic and belongs to the benzimidazole group of medicines. In order to achieve better medicinal results, i.e. enhanced activity and low toxicity, structural modifications are made in the existing drugs. Some 5-benzoyl-N-[1-(alkoxyphthalimido) benzimidazol-2-yl] carbamic acid methyl ester (3a-c) and 5-benzoyl-N-[1-(2,3-bis oxyphthalimido∕oxysuccinimido propyl benzimidazol-2-yl) carbamic acid methyl ester (7a-b) have been synthesized from two different routes. Structures of the compounds have been established on the basis of elemental analysis and spectral studies. All the synthesized compounds (3a-c) and (7a-b) were assayed in vitro for antimicrobial activity against mebendazole (itself) and standard [ciprofloxacin (antibacterial) and fluconazole (antifungal)]