02706nas a2200277   4500008004100000022001400041245017600055210006900231260000800300300001100308490000900319520169400328653002402022653002802046653002102074653005102095653001502146653002202161653003402183100002102217700002402238700003202262700000502294700000502299856012402304       2020                        eng d  a0304-416500aNADP-dependent glutamate dehydrogenases in a dimorphic zygomycete Benjaminiella poitrasii: purification, characterization and their evaluation as an antifungal drug target0 aNADPdependent glutamate dehydrogenases in a dimorphic zygomycete  cNOV  a1296960 v18643 a<p>Background: It has been reported that the genes coding for NADP-dependent glutamate dehydrogenases (NADP-GDHs) showed a cause-effect relationship with Yeast-Hypha (Y-H) reversible transition in a zygomycete Benjaminiella poitrasii. As Y-H transition is significant in human pathogenic fungi for their survival and proliferation in the host, the NADP-GDHs can be explored as antifungal drug targets. Methods: The yeast-form specific BpNADPGDH I and hyphal-form specific BpNADPGDH II of B. poitrasii were purified by heterologous expression in E. coll. BL-21 cells and characterized. The structural analogs of L-glutamate, dimethyl esters of isophthalic acid (DMIP) and its derivatives were designed, synthesized and screened for inhibition of NADP-GDH activity as well as Y-H transition in B. poitrasii, and also in human pathogenic Candida albicans strains. Results: The BpNADPGDH I and BpNADPGDH II were found to be homo-hexameric proteins with native molecular mass of 282 kDa and 298 kDa, respectively and subunit molecular weights of 47 kDa and 49 kDa, respectively. Besides the distinct kinetic properties, BpNADPGDH I and BpNADPGDH II were found to be regulated by cAMP-dependent- and Calmodulin (CaM) dependent- protein kinases, respectively. The DMIP compounds showed a more pronounced effect on H-form specific BpNADPGDH II and inhibited Y-H transition as well as growth in B. poitrasii and C. albicans strains. Conclusion: The present study will be useful to design and develop antifungal drugs against dimorphic human pathogens using glutamate dehydrogenase as a target. Significance: Glutamate dehydrogenases can be explored as a target against human pathogenic fungi.</p>
10aAntifungal compound10aBenjaminiella poitrasii10aCandida albicans10aDimethyl esters and amides of isophthalic acid10adimorphism10aEnzyme inhibition10aNADP-glutamate dehydrogenases1 aPathan, Ejaj, K.1 aKulkarni, Anand, M.1 aPrasanna, Nallaballe, V. L.1 a1 a  uhttps://library.ncl.res.in/content/nadp-dependent-glutamate-dehydrogenases-dimorphic-zygomycete-benjaminiella-poitrasii01487nas a2200193   4500008004100000022001400041245009500055210006900150260000800219300001600227490000600243520081100249100002301060700000501083700003101088700002301119700002601142856012501168       2021                        eng d  a2470-134300aNew 1,2,3-triazole-appended bis-pyrazoles: synthesis, bioevaluation, and molecular docking0 aNew 123triazoleappended bispyrazoles synthesis bioevaluation and  cSEP  a24879-248900 v63 aThe present work describes design of a small library of new 1,2,3-triazole-appended bis-pyrazoles by using a molecular hybridization approach, and the synthesized hybrids were evaluated for their antifungal activity against different fungal strains, namely, Candida albicans, Cryptococcus neoformans, Candida glabrata, Candida tropicalis, Aspergillus niger, and Aspergillus fumigatus. All the compounds exhibited broad-spectrum activity against the tested fungal strains with excellent minimum inhibitory concentration values. The molecular docking study against sterol 14 alpha-demethylase (CYP51) could provide valuable insights into the binding modes and affinity of these compounds. Furthermore, these compounds were also evaluated for their antioxidant activity, which also resulted in promising data.1 aDanne, Ashruba, B.1 a1 aSangshetti, Jaiprakash, N.1 aKhedkar, Vijay, M.1 aShingate, Bapurao, B.  uhttps://library.ncl.res.in/content/new-123-triazole-appended-bis-pyrazoles-synthesis-bioevaluation-and-molecular-docking