Self-assembly of chiral BINOL cages via imine condensation.

Condensation of an (S)- or (R)-BINOL-derived dialdehyde and tris(2-aminoethyl)amine produced chiral [2+3] imine cages, which were further reduced to furnish more stable chiral amine cages and applied in the enantioselective recognition of (1R,2R)- and (1S,2S)-1,2-diaminocyclohexane.

Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling.

Augmenting glucose utilization and energy expenditure in skeletal muscle via AMP-activated protein kinase (AMPK) is an imperative mechanism for the management of type 2 diabetes. Chemical derivatives (2a-2h, 3, 4a-4d, 5) of the isoalantolactone (K007), a bioactive molecule from roots of Inula racemosa were synthesized to optimize the bioactivity profile to stimulate glucose utilization in skeletal muscle cells. Interestingly, 4a augmented glucose uptake, driven by enhanced translocation of glucose transporter 4 (GLUT4) to cell periphery in L6 rat skeletal muscle cells. The effect of 4a was independent to phosphatidylinositide-3-kinase (PI-3-K)/Akt pathway, but mediated through Liver kinase B1 (LKB1)/AMPK-dependent signaling, leading to activation of downstream targets acetyl coenzyme A carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c). In db/db mice, 4a administration decreased blood glucose level and improved body mass index, lipid parameters and glucose tolerance associated with elevation of GLUT4 expression in skeletal muscle. Moreover, 4a increased energy expenditure via activating substrate utilization and upregulated the expression of thermogenic transcription factors and mitochondrial proteins in skeletal muscle, suggesting the regulation of energy balance. These findings suggest the potential implication of isoalantolactone derivatives for the management of diabetes.

Quercetin-6-C-ß-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor.

Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-ß-D-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells.

Antimycotic susceptibility testing of agents of black grain eumycetoma.

Antimycotic susceptibility testing of 17 strains of eumycetes including Madurella mycetomatis, Madurella grisea, Pyrenochaeta romeroi, Exophiala jeanselmei and Leptosphaeria tompkinsii, isolated from cases of black grain mycetoma, was carried out against ketoconazole, itraconazole, miconazole and econazole by broth microdilution and agar dilution methods. Itraconazole and ketoconazole were more active inhibiting 50% of the strains (MIC 50) at 0.5 and 1 microgram ml-1 and 90% (MIC 90) at 2.5 and 5 micrograms ml-1, respectively. The MIC 50s of econazole and miconazole were 2.5 and 5 micrograms ml-1 and MIC 90s 10 micrograms ml-1 for both drugs.

Mycotic keratitis in Madras.

Corneal scrapings from 698 clinically suspected cases of mycotic keratitis were investigated for evidence of fungal infection. Of these, 322 were found to be positive by direct examination and/or culture. The infection was predominantly seen in the age group 21-50. Men were more frequently affected than women. Majority of the patients were either agricultural workers or out door manual labourers and 66.8% of them gave a definite history of antecedent corneal trauma due to vegetable or soil matter. Asperyllus flavus was the commonest causal agent isolated from 55 cases (17.1%), followed by A. niger (13.7%), A. fumigatus (10.9%), A. terreus (1.2%), A. glaucus (0.9%), and Pseudoallescheria boydii (0.6%). The order of occurrence of the genera of fungi isolated was Aspergillus, Acremonium, Curvularia, Fusarium, Candida, Syncephalastrum, Penicillium, Aureobasidium, Drechslera, Cladosporium, Rhizopus, Alternaria, Mucor, Pseudoallecheria and lastly Paecilomyces and Trichoderma from one case each.