A novel imidazole nucleoside containing a diaminodihydro-S-triazine as a substituent: inhibitory activity against the West Nile virus NTPase/helicase

The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2'-deoxy-beta-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2'-deoxy-beta-D-erythropentofuranosyl)-5-(2, 4-diamino-3, 6-dihydro-1,3, 5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/helicase with an IC50 of 3-10 microg/mL.     

Synthesis of 1,2,4-triazole-linked urea/thiourea conjugates as cytotoxic and apoptosis inducing agents

A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been synthesized and evaluated for their in vitro cytotoxicity against selected human cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference drug. The compound 5t showed significant cytotoxicity on MCF-7 breast cancer cell line with a IC₅₀ value of 7.22?±?0.47?µM among all the tested compounds. Notably, induction of apoptosis by compound 5t on MCF-7 cells was evaluated using different staining techniques such as acridine orange/ethidium bromide (AO/EB), annexin V-FITC/PI, and DAPI. Further, clonogenic assay indicates the inhibition of colony formation on MCF-7 cells by compound 5t. Moreover, the flow-cytometric analysis also revealed that compound 5t caused the arrest of cells at G0/G1 phase of cell cycle. In addition, the compounds when tested on normal human cells (L-132) were found to be safer with low cytotoxicity profile.     

Distribution and trafficking of JHM coronavirus structural proteins and virions in primary neurons and the OBL-21 neuronal cell line.

The neurotropic murine coronavirus JHM is capable of inducing various forms of neurologic diseases, including demyelination. Neurons have been shown to act as a repository site at the early stages of the disease process (O. Sorensen and S. Dales, J. Virol. 56:434-438, 1985). JHM virus (JHMV) replication and trafficking of viral proteins and virions in cultured rat hippocampal neurons and a neuronal cell line, OBL-21, were examined, with an emphasis placed on the role of the microtubular network. We show here that JHMV spread within the central nervous system occurs transneuronally and that virus protein trafficking was dependent upon microtubules. Viral trafficking occurred asymmetrically, involving both the somatodendritic and the axonal domains. Thus coronavirus can be disseminated from neurons at either the basolateral or the apical domains. A specific interaction between antibodies derived against the microtubule-associated protein tau and JHMV nucleocapsid protein (N) was observed, which can presumably be explained by an overall amino acid similarity of 44% and an identity of 20% between proteins N and tau, with optimal alignment at the microtubule binding domain of tau. Collectively, our data suggest an important role of the microtubule network in viral protein trafficking and distribution. They also draw attention to protein sequence mimicry of a cell component by this coronavirus as one strategy for making use of the host's functions on behalf of the virus.     

in vitro inhibition of the measles virus by novel ring-expanded ('fat') nucleoside analogues containing the imidazo[4,5-e]diazepine ring system

The synthesis and in vitro anti-measles virus (anti-MV) activity of a class of ring-expanded ('fat') nucleoside analogues (1-4) containing the title heterocyclic ring system are reported. The target compounds were synthesized by base-catalyzed condensations of 4,5-dicarboxylic acid esters of the appropriately substituted imidazole-1-ribosides with suitably substituted guanidine derivatives. Compounds were screened for anti-MV activity in African green monkey kidney cells (CV-1), employing ribavirin as the control standard. While the parent compound 1 itself failed to show any significant antiviral activity against MV, its analogues containing hydrophobic substituents at the 2-position (2) or the 6-position (4) showed promising antiviral activity at submicromolar or micromolar concentration levels with no apparent toxicity to the host cell line. Both compounds showed higher anti-MV activity than the control drug ribavirin.     

Genetic and functional diversity among root-associated psychrotrophic Pseudomonad’s isolated from the Himalayan plants

Out of 534 psychrotrophic bacteria, 12 bacteria were selected on the basis of plant growth promoting activities at 4 °C and identified as Pseudomonas genus. These strains showed high level of genetic polymorphisms based on RAPD and rep-PCR fingerprinting. This genetic variability revealed that isolates belonging to same species were as high as the variability among different species. Further inoculation of these Pseudomonas strains significantly improves root/shoot biomass and nutrients uptake of lentil plant as compared to non-bacterized control after 40 days of seed showing. Agglomerative hierarchical clustering analysis of pot assay results revealed that genetically diverse strains showing the same prototype in functional parameter and representing diverse blueprint of plant growth promoting attributes. Results of present findings explain the huge beneficial microbial resources from root zone of hilly crops of Himalayan region that could be effectively exploited as bio-inoculums for cold climatic condition.