Synthesis, molecular docking and ADME studies of thiazole-thiazolidinedione hybrids as antimicrobial agents.

New thiazole-thiazolidinedione hybrids (5a-k) were efficiently synthesized and evaluated for their in-vitro antimicrobial activity against four fungal and bacterial strains. The chemical structures of the compounds were elucidated by FTIR, 1H NMR, and 13C NMR spectral data. Most of the synthesized compounds were sensitive against gram positive, gram negative bacterial and fungal strains. Among the synthesized molecules, compounds 5h, and 5i exhibited promising inhibitory activity against all selected fungal strains and gram positive bacteria namely, Staphylococcus aureus, and Enterococcus faecalis. The molecular docking results predicted that the thiazole-thiazolidinedione derivatives bind to the active site protein ATP-binding pocket from E. coli, S. aureus and C. albicans with good interaction energy scores. Ct-DNA was used to evaluate the binding interactions of the selected compounds by means of absorption spectroscopy. To further characterize the drug-likeness and ADME properties were calculated using the Qikprop, the result of present study suggests that thiazole-thiazolidinedione hybrid could be an interesting approach for the design of new antimicrobial agents.Communicated by Ramaswamy H. Sarma.

Quinoline-azetidinone hybrids: Synthesis and in vitro antiproliferation activity against Hep G2 and Hep 3B human cell lines.

In search of new heterocyclic anticancer agents, a new quinoline-azetidinone hybrid template have been designed, synthesized and screened for their cytotoxic activity against human cancer cell lines such as Hep G2, and Hep 3B by the MTT assay and results were compared with paclitaxel, 5-fluorouracil and doxorubicin. Interestingly, some of the compounds were found significantly active against both cell lines. The compound 6f (IC50=0.04±0.01µM) exhibited potent antiproliferation activity against Hep G2 cell line, and 6j compound (IC50=0.66±0.01µM) demonstrated potent antiproliferation activity against Hep 3B cell line and provide to be more potent as cytotoxic agents than standard drugs. Morphological changes suggest the induction of apoptosis and describe the mechanism of action of these hybrid antitumor agents.

Synthesis of novel pyrazole­thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors.

A series of 1,3,4-trisubstituted pyrazole derivatives (3 a-f), (4 a-f), and (5 a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 µM. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 µM), with a significant selectivity index (SI > 60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents.

1,3,4-Trisubstituted pyrazole analogues as promising anti-inflammatory agents.

Twenty-two 1,3,4-trisubstituted pyrazole (3a-d), (4a-d), (5a-d), (6a-l) derivatives were synthesized and structure of newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, and mass spectral analysis. These compounds were screened for the anti-inflammatory activity by carrageenan-induced paw edema method. Compounds 5a, and 5b showed excellent anti-inflammatory activity (⩾84.2% inhibition) and 3a, 3b, and 3c showed good anti-inflammatory activity (⩾64.6% inhibition) compared to that of the standard drug diclofenac (86.72%) when measured 3h after the carrageenan injection. Moreover, the cyclooxygenase (COX) enzyme inhibitor activity of selected compounds, which are the excellent anti-inflammatory activities in carrageenan-induced paw edema model, was investigated in vitro COX inhibition assay. Molecular docking study further helped in supporting the observed activity. In addition compound 5a exhibited considerable cytotoxic activity against MCF-7 cell line with IC50 value 6.5 µM.

Synthesis and antitubercular activity of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives.

Novel 3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives were efficiently synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB). The chemical structures of the compound were elucidated by elemental analysis, FTIR, (1)H NMR, and mass spectral data. Most of the title compounds have exhibited significant antitubercular activity. Compounds 4g, 4h, 4l, 4n and 4o showed pronounced antitubercular activity comparable to the reference isoniazid, whereas, compounds 4a, 4c, 4j, 4k, and 4p displayed good antitubercular activity. 5-(4-chlorophenyl)-4,5-dihydro-3-p-tolylpyrazol-1-yl-(6-methylimidazo[2,1-b]thiazol-5-yl)methanone (4g) was found to be the most promising compound with MIC values of 0.39 µg/ml.

Anti-obesity effects of galangin, a pancreatic lipase inhibitor in cafeteria diet fed female rats.

CONTEXT: Alpinia galanga Willd (Zingiberaceae) (AG) is a rhizomatous herb widely cultivated in shady regions of Malaysia, India, Indochina and Indonesia. It is used in southern India as a domestic remedy for the treatment of rheumatoid arthritis, cough, asthma, obesity, diabetes, etc. It was reported to have anti-obesity, hypoglycemic, hypolipidemic and antioxidant properties. OBJECTIVE: A flavonol glycoside, galangin, was isolated from AG rhizomes. Based on its in vitro pancreatic lipase inhibitory effect, the study was further aimed to clarify whether galangin prevented obesity induced in female rats by feeding cafeteria diet (CD) for 6 weeks. MATERIALS AND METHODS: The in vitro pancreatic lipase inhibitory effect of galangin was determined by measuring the release of oleic acid from triolein. For in vivo experiments, female albino rats were fed CD with or without 50 mg/kg galangin for 6 weeks. Body weight and food intake was measured at weekly intervals. On day 42, serum lipids levels were estimated and then the weight of liver and parametrial adipose tissue (PAT) was determined. The liver lipid peroxidation and triglyceride (TG) content was also estimated. RESULTS: The IC50 value of galangin for pancreatic lipase was 48.20 mg/mL. Galangin produced inhibition of increased body weight, energy intake and PAT weight induced by CD. In addition, galangin produced a significant decrease in serum lipids, liver weight, lipid peroxidation and accumulation of hepatic TGs. CONCLUSION: Galangin present in AG rhizomes produces anti-obesity effects in CD-fed rats; this may be mediated through its pancreatic lipase inhibitory, hypolipidemic and antioxidant activities.

Effect of Argyreia speciosa root extract on cafeteria diet-induced obesity in rats.

OBJECTIVES: To evaluate the antiobesity effects of the ethanolic extract of Argyreia speciosa roots in rats fed with a cafeteria diet (CD). MATERIALS AND METHODS: Obesity was induced in albino rats by feeding them a CD daily for 42 days, in addition to a normal diet. Body weight and food intake was measured initially and then every week thereafter. On day 42, the serum biochemical parameters were estimated and the animals were sacrificed with an overdose of ether. The, liver and parametrial adipose tissues were removed and weighed immediately. The liver triglyceride content was estimated. The influence of the extract on the pancreatic lipase activity was also determined by measuring the rate of release of oleic acid from triolein. RESULTS: The body weight at two-to-six weeks and the final parametrial adipose tissue weights were significantly lowered (P < 0.01 and P < 0.05, respectively) in rats fed with the CD with Argyreia speciosa extract 500 mg/kg/day as compared to the CD alone. The extract also significantly reduced (P < 0.01) the serum contents of leptin, total cholesterol, low density lipoprotein (LDL), and triglycerides, which were elevated in rats fed with CD alone. In addition, the extract inhibited the induction of fatty liver with the accumulation of hepatic triglycerides. The extract also showed inhibition of pancreatic lipase activity by using triolein as a substrate. CONCLUSIONS: The ethanolic extract of Argyreia speciosa roots produces inhibitory effects on cafeteria diet-induced obesity in rats.

Effect of Moringa oleifera Lam. root-wood on ethylene glycol induced urolithiasis in rats.

In India, drumstick (Moringa oleifera Lam. (Moringaceae)) is commonly used as a phytotherapeutic agent. The effect of oral administration of aqueous and alcoholic extract of Moringa oleifera root-wood on calcium oxalate urolithiasis has been studied in male Wistar albino rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. Supplementation with aqueous and alcoholic extract of Moringa oleifera root-wood significantly reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in the kidneys of calculogenic rats was also significantly lowered by curative and preventive treatment using aqueous and alcoholic extracts. The results indicate that the root-wood of Moringa oleifera is endowed with antiurolithiatic activity.