Conversion of carbonimidodithioates to carbamates

Carbonimidodithioates derived from primary amines or α-amino acid esters have been converted to N-benzyloxycarbonyl derivatives under mild conditions by treatment first with sodium benzyl alcoholate and then with water. N-Benzyloxycarbonyl α-amino acids have been generated from the methyl esters by alkaline hydrolysis or from the allyl esters by Pd0-catalysed de-allylation

Reaction of lactim ethers and lactim sulfides with electrophiles: attackat nitrogen followed by ring-opening under neutral conditions

Electrophilic push-pull molecules react at the nitrogen of lactim ethers and lactim sulfides; subsequent hydrolysis gives ring-opened products in good yields

Conversion of carbonimidodithioates into unsymmetrical di- and tri- substituted ureas including urea dipeptides

Selective hydrolysis of carbonimidodithioates (3) leads to the thiocarbamates (4), which can be easily transformed to the unsymmetrical ureas (5) by treatment with the appropriate amines. This constitutes a synthesis of ureas without the use of phosgene or carbon monoxide

In Vivo Investigations of Selected Diamidine Compounds against Trypanosoma evansi Using a Mouse Model ▿

Surra is an animal pathogenic protozoan infection, caused by Trypanosoma evansi, that develops into a fatal wasting disease. Control measures rely on diagnosis and treatment. However, with the continuous emergence of drug resistance, this tactic is failing, and the pressing need for new chemotherapeutic agents is becoming critical. With the introduction of novel aromatic diamidines, a new category of antitrypanosomal drugs was discovered. Nevertheless, their efficacy within a T. evansi-infected mouse model was not known. In total, 30 compounds previously selected based on their in vitro activity were tested in a T. evansi mouse model of infection. Six of the compounds were capable of curing T. evansi-infected mice at drug doses as low as 0.5 and 0.25 mg/kg of body weight administered for 4 consecutive days, and they were more effective than the standard drugs suramin, diminazene, and quinapyramine. After all selection criteria were applied, three diamidine compounds (DB 75, DB 867, and DB 1192) qualified as lead compounds and were considered to have the potential to act as preclinical candidates against T. evansi infection

Not Available

Not AvailableInfectious laryngotracheitis (ILT) is one of the highly infectious and contagious diseases of chickens caused by Gallid Herpesvirus 1, a member of the genus Iltovirus. It is an economically important disease in major poultry producing countries, including India. Despite India having large population of poultry birds, very limited information is available on the disease magnitude and molecular epidemiology. We screened 560 tissue samples collected from necropsied cases of tracheitis and conjunctivitis to diagnose ILT by histopathology, immunohistochemistry and polymerase chain reaction. Out of 560 samples, ILT was diagnosed in 90 (16.07%) cases by histopathology; however, polymerase chain reaction detected ILT virus (ILTV) in 128 (22.85%). Immu-nohistochemistry of representative PCR positive tissues (n=30) from trachea, lungs and conjunctiva detected viral antigen in the lining or denuded epithelial cells in 76.66% (23/30) cases. Analysis of age wise occurrence of ILT cases in our study revealed 47.65% in adult birds over 18 weeks of age, 35.15% in grower birds aged between 7 and18 weeks of age, 17.18% in chicks aged less than 6 weeks. Nucleotide sequence of gene encoding viral thymidine kinase revealed involvement of vaccine and virulent strains of ILTV in the investigated cases. Based on our findings and recent publications, we conclude that there is resurgence or re-emergence of ILT in the chicken flocks in different parts of India, indicating a possible biosecurity breach. Further genetic characterization of virus by whole genome sequencing technologies would decipher the genotype circulating in India, and help to design suitable native vaccine candidate(s).Not Availabl

Not Available

Not AvailableWe describe the first report on spontaneous Avian Nephritis Virus (ANV) and Infectious Bronchitis Virus (IBV) concurrent infection in broiler chicks. On necropsy, the kidneys were found swollen with its parenchyma and ureters stuffed with urate flakes. Histopathologically, the renal tubular damage and inflammatory response were severe in concurrently infected birds compared to the cases infected only with ANV, which had direct correlation with significantly (p < 0.001) increased expression of IL-1 β, IL-4, IL-12, IL-13, iNOS and IFN-γ transcripts in the kidneys of concurrently infected birds. Relative decrease in IFN-β transcript levels in the concurrently infected birds indicates suppression of antiviral response; the iNOS level was manifold increased which can be attributed to the enhanced macrophage response. Nucleotide sequencing of S1-spike glycoprotein gene of IBV and RNA dependent RNA polymerase gene of ANV confirmed etiologies as Igacovirus of Gammacoronavirus and ANV-2 of Avastrovirus 2, respectively. Both ANV and IBV virus affect kidneys. Our findings suggested that concurrent infections of these two viruses might have enhanced the transcripts of Th1, Th2 and proinflammatory cytokines with reduced IFN-β transcripts resulting in decreased host innate antiviral mechanisms leading to exacerbated renal lesions. Future experimental co-infection studies could throw more lights on pathology and pathogenesis during concurrent infections of ANV and IBV in poultry.Not Availabl

Not Available

Not AvailableSalmonella species are Gram-negative bacteria with more than 2600 serovars. Among these serovars, many are associated with various diseases in livestock and humans. White Kauffman Le-Minor (WKL) serotyping scheme applies specific serum to determine the serovars of Salmonella. Recent studies have applied molecular methods for serovar predictions. These methods include PCR, hybridization and sequence data to detect/predict serovar-specific genetic elements. Among these, PCR is a robust method if the unique genetic element is already known. Within this context, also involving novel primers, two multiplex PCR assays were standardized to detect six important Salmonella serovars viz. Typhimurium, Enteritidis, Kentucky, Infantis, Virchow and Gallinarum associated with poultry in India. The developed PCR assays showed targeted serovar specificity. Serial dilution experiments of both kit-based and crude lysate DNA preparations indicated similar applicability of both methods for testing from pure cultures. Further the developed assays were validated with 25 recent field isolates to confirm the applicability in routine diagnosis. The PCR assay could predict all the targeted serovars (17/25) with 100% specificity (CI-95%; 0.63-1). Molecular serotyping can reduce the number of serum used incomparison to the conventional serotyping which involves more random application of serum.Not Availabl

Diphenyl Furans and Aza Analogs: Effects of Structural Modification on In Vitro Activity, DNA Binding, and Accumulation and Distribution in Trypanosomes▿

Human African trypanosomiasis is a devastating disease with only a few treatment options, including pentamidine. Diamidine compounds such as pentamidine, DB75, and DB820 are potent antitrypanosomal compounds. Previous investigations have shown that diamidines accumulate to high concentrations in trypanosomes. However, the mechanism of action of this class of compounds remains unknown. A long-hypothesized mechanism of action has been binding to DNA and interference with DNA-associated enzymes. The fluorescent diamidines, DB75 and DB820, have been shown to localize not only in the DNA-containing nucleus and kinetoplast of trypanosomes but also to the acidocalcisomes. Here we investigate two series of analogs of DB75 and DB820 with various levels of in vitro antitrypanosomal activity to determine whether any correlation exists between trypanosome accumulation, distribution, and in vitro activity. Despite wide ranges of in vitro antitrypanosomal activity, all of the compounds investigated accumulated to millimolar concentrations in trypanosomes over a period of 8 h. Interestingly, some of the less potent compounds accumulated to concentrations much higher than those of more potent compounds. All of the compounds were localized to the DNA-containing nucleus and/or kinetoplast, and many were also found in the acidocalcisomes. Accumulation in the nucleus and kinetoplast should be important to the mechanism of action of these compounds. The acidocalcisomes may also play a role in the mechanism of action of these compounds. This investigation suggests that the extent of accumulation alone is not responsible for killing trypanosomes and that organelle-specific accumulation may not predict in vitro activity