Synthesis and biological evaluation of trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxyalkylamine derivatives against drug susceptible,non-replicating M. tuberculosis H37Rv and clinical multidrug resistant strains

Synthesis of a library of novel trans 6-methoxy-1,1-dimethyl-2-phenyl-3-aryl-2,3-dihydro-1H-inden-4-yloxy alkyl amines and their antimycobacterial activity against drug sensitive and multidrug resistant strains of Mycobacterium tuberculosis have been reported. All the new compounds in the series exhibited MIC between 1.56 and 6.25 μg/ml. Two compounds 1i and 1j with low MIC and low cytotoxicity showed significant reduction in CFU in infected mouse macrophages at 1× MIC concentration. The compound 1i inhibited the growth of M. tuberculosis in mice at 100 mg/kg dose with 1.35 log₁₀ reduction of CFU in lungs tissue and was active against non-replicating Mycobacterium tuberculosis under anaerobic condition.     

Quantitative structure activity relationship studies on 3-triazines using van der Waal volume and molecular connectivity index

QSAR studies have been performed on the homologues of 3-triazines, using molecular connectivity index and van der Waal volume as structural parameters. The regression analysis has shown good correlation between antitumour activity and the two structural parameters.     

ISOLATION AND CHARACTERIZATION OF CHROMATIN FROM NEUROSPORA CRASSA

Different preparations of chromatin isolated from mycelia of Neurospora crassa were analyzed for DNA-associated RNA and proteins. The UV absorption spectra, the ultrastructure of chromatin, and the amino acid composition of the acid-extractable proteins were studied. The protein:DNA ratios range from 1.5 to 2.8; the RNA:DNA ratios range from 0.5 to 1.24. UV absorption shows a macimum at 259 mµ and a minimum at 238–239 mµ. The E280/E260 ranges from 0.59 to 0.70. Electron microscopy reveals a fibrous structure with individual fibers of 120–150 A average diameter. Attempts were made to study the protein by polyacrylamide gel electrophoresis and amino acid analysis. The results indicate that Neurospora chromatin does not contain basic proteins comparable to calf thymus histone. The ratios of basic to acidic amino acids range from 0.93 to 1.19. On electrophoresis, no bands are seen whose positions correspond to those of histones. Staining for basic proteins with fast green or eosin Y at pH 8.2 also shows a negative reaction, suggesting the absence of histones.     

Potential use of the essential oil ofTrachyspermum ammi against seed-borne fungi of Guar (Cyamopsis tetragonoloba L. (Taub.))

Essential oils isolated from leaves and seeds of seven umbelliferous plants were tested against the growth ofAspergillus flavus. Those from seeds ofTrachyspermum ammi, Cuminum cyminum, Carum carvi, Daucus carota and from leaves ofAnethum graveolens exhibited antifungal activity against the test fungus. Amongst these, oil from seeds ofTrachyspermum ammi was most toxic. Its minimum inhibitory concentration was 300 ppm, at which it exhibited fungistatic but not phytotoxic properties, when tested at 200, 300 and 400 ppm. The fungitoxic potency ofTrachyspermum seed oil remained unchanged after a long storage period and at high inoculum density of the test fungus. The oil was thermostable and was more efficaceous than the fungicides Agrosan G.N., Benlate, Ceresan, Dithane M-45 and Thiovit commonly used for the control of plant diseases.     

Interaction of the carboxamide of NADPH with Lactobacillus casei dihydrofolate reductase

Dihydrofolate reductase from Lactobacillus casei and its complexes with NADPH and methotrexate yield well-resolved Raman spectra. The 1685-cm^?1 Raman band assigned to the carboxamide of NADPH persists in the NADPH-enzyme binary complex but is absent from the NADPH-methotrexate-enzyme ternary complex. This is ascribed to stabilization of the polarized form of the carboxamide by H bonding to the NH and CO groups of Ala 6 and Ile 13 of the peptide backbone.     

Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)‐induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA‐induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA‐induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains‐containing protein 3; NLRP3, apoptosis‐associated speck like protein containing a caspase recruitment domain; ASC, caspase‐1, nuclear factor‐kappa B; NF‐κB, interleukin‐6), fibrogenic makers (α‐smooth muscle actin; ɑ‐SMA, transforming growth factor; TGF‐β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid‐derived 2)‐like factor 2; Nrf2, superoxide dismutase‐1; SOD‐1, catalase). The present findings concluded that DMF protects against TAA‐induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.