https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30110 50 values in the cell proliferation assay, CEP701 was the most potent inhibitor; sunitinib and PKC412 were ranked second and third, respectively. Sunitinib was the most selective inhibitor, followed by PKC421 and CEP701. The potency of sunitinib and to a lesser extent CEP701 in inhibition of FLT3 autophosphorylation was lower than the cell proliferation inhibition, indicating that inhibition of FLT3 downstream proteins may contribute to the cellular effects. It was shown in this study that the docking procedure was able to differentiate FLT3 inhibitors from ineffective compounds. Additionally, interaction with the phosphate binding region in the ATP-binding pocket increased potency at the cost of selectivity. These findings can be applied in designing highly effective and selective inhibitors for FLT3 and other related kinases.]]> Wed 15 Dec 2021 16:10:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29353 70/σ^A interaction as determined by ELISA and exhibiting increased inhibition of the growth of Escherichia coli compared to Bacillus subtilis in culture. The structural features of the synthesized transcription initiation inhibitors needed for antibacterial activity were identified employing molecular modelling and structure–activity relationship (SAR) studies.]]> Wed 15 Dec 2021 16:09:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47118 Wed 14 Dec 2022 12:25:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:14134 1D- subtype compared to α_1A- and α_1B-ARs. 9 out of 12 of the tested compounds displayed affinity at the α_1A and α_1D -AR subtypes and 6 displayed affinity at all three α₁-AR subtypes, no α_1B-AR selective compounds were identified. 8 of the 9 compounds with α₁-AR affinity were antagonists and one compound displayed partial agonist characteristics. This virtual screening has successfully identified an α_1A/D-AR selective antagonist, with low µM affinity with a novel structural scaffold of a an isoquinoline fused three-ring system and good lead-like qualities ideal for further drug development.]]> Wed 11 Apr 2018 14:43:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:30559 70/σ^A interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library of structurally diverse compounds was examined by enzyme-linked immunosorbent assay (ELISA) to assess the inhibition of the targeted protein–protein interaction. Inhibition of bacterial growth was also evaluated using Bacillus subtilis and Escherichia coli cultures. The structure–activity relationship studies demonstrated the significance of particular structural features of the synthesized molecules for RNA polymerase-σ⁷⁰/σ^A interaction inhibition and antibacterial activity. Docking was investigated as an in silico method for the further development of the compounds.]]> Wed 09 Mar 2022 16:04:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8305 Sat 24 Mar 2018 08:40:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7206 Sat 24 Mar 2018 08:39:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3009 Sat 24 Mar 2018 08:33:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3031 Sat 24 Mar 2018 08:30:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1483 Sat 24 Mar 2018 08:28:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:14589 Sat 24 Mar 2018 08:20:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10405 Sat 24 Mar 2018 08:07:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20055 70/σ^A for the development of lead molecules exhibiting a novel mechanism of antibacterial activity. Several classes of structurally related bis-indole inhibitors of bacterial transcription initiation complex formation were synthesized and their antimicrobial activities were evaluated. Condensation of indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis of 7,7′-, 2,2′-, 2,7′- and 3,2′-linked bis-indole derivatives with –CO–NH–NH–CO– and –CO–CO–NH–NH–CO– linkers. Indole-7-glyoxyloyl chlorides were reacted with hydrazine hydrate in different ratios to afford respective –CO–CO–NH–NH–CO–CO– bis-indole or hydrazide derivatives. The resulting compounds were found to be active against the β′-CHσ⁷⁰/σ^A_2.2 interaction in ELISA assays and inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure–activity relationship (SAR) studies were performed in order to identify the structural features of the synthesized inhibitors required for biological activity.]]> Sat 24 Mar 2018 08:00:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:19931 Sat 24 Mar 2018 07:58:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:19252 Sat 24 Mar 2018 07:54:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:21263 1B adrenoceptor replacing the charged aspartate, D191, as well as a potential interaction partner, K331, with uncharged alanines to observe effects on ligand binding and receptor activation. Significant 4–6 fold reductions in affinity for the endogenous agonists, epinephrine and norepinephrine were observed for receptors with the D191A mutation in the second extracellular loop. While changes in EC₅₀ were observed, operational analysis yielded no apparent change in receptor activation. Based on these findings, we suggest that D191, in the second extracellular loop of the α_1B adrenoceptor, acts as a ‘point of first contact’ for the receptor׳s endogenous agonists. Implication of the non-conserved extracellular regions of the receptor in agonist binding makes it a potential target for the design of highly selective drugs.]]> Sat 24 Mar 2018 07:54:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20965 Sat 24 Mar 2018 07:54:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20167 Sat 24 Mar 2018 07:51:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5529 Sat 24 Mar 2018 07:46:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:295 Sat 24 Mar 2018 07:43:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:374 Sat 24 Mar 2018 07:42:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27697 70/σ^A factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ⁷⁰/σ^A interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.]]> Sat 24 Mar 2018 07:40:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3457 Sat 24 Mar 2018 07:20:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3428 Sat 24 Mar 2018 07:20:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4868 Sat 24 Mar 2018 07:18:43 AEDT ]]>