https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37670 Wed 22 Mar 2023 17:08:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27267 Wed 17 Nov 2021 16:32:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47111 Wed 14 Dec 2022 10:19:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38373 80% of 18 samples as having short, medium or long telomeres compared with 33–72% using other methods.]]> Wed 01 Sep 2021 12:47:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38461 50=30 nM and 400-fold selective c.f. MCF10A (normal breast tissue). Acetamide moiety modification (13 a-g) to introduce additional hydrophobicity was favoured with MCF-7 breast cancer cell activity enhanced at 1.3 nM. Other analogues were potent against the HT29 colon cancer cell line at 23 nM. Textbook SAR data was observed in the MCF-7 cell line, in an MTT assay, via the ortho (17 a), meta (17 b) and para (13 f). The amino alcohol -OH moiety was pivotal, but no stereochemical preference noted. But, these data did not fit our homology modelling expectations. Aberrant MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) screening results and metabolic interference confirmed by sulforhodamine B (SRB) screening. Interfering analogues resulted in 120 and 80-fold CYP1A1 and CYP1A2 amplification, with no upregulation of SULT1A1. This is consistent with activation of the AhR pathway. Piperidine per-deuteration reduced metabolic inactivation. 3-OH / 4-OH piperidine analogues showed differential MTT and SRB activity supporting MTT assay metabolic inactivation. Data supports piperidine 3-OH, but not the 4-OH, as a CYP substrate. This family of β-amino alcohol substituted 3,4-dichlorophenylacetonitriles show broad activity modulated via the AhR pathway. By SRB analysis the most potent analogue was 23 b, (Z)-3-(4-(3-(4-phenylpiperidin-1-yl)-2-hydroxypropoxy)phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile.]]> Thu 18 Nov 2021 10:32:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7404 Sat 24 Mar 2018 08:42:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8093 Sat 24 Mar 2018 08:34:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12397 50s of 25–40 μM. The high ‘hit rate’ (5.6%) indicates that the approach taken here has advantages over conventional drug screening methods. A major advantage of norcantharidin analogues over some other currently available anthelmintics is that they can be produced in one to two steps in large amounts at low cost and high purity, and do not require any additional steps for the isolation of the active isomer. This positions them well for commercial development.]]> Sat 24 Mar 2018 08:15:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11336 Sat 24 Mar 2018 08:13:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10855 Sat 24 Mar 2018 08:12:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17425 Sat 24 Mar 2018 08:01:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17424 Sat 24 Mar 2018 08:01:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20489 25 fold) and 13 (5.7 to >80 fold). Other analogues show high level of efficacy against specific cell lines with 10 showing excellent activity against MCF-7 (GI₅₀ = 1.7 µM) and A431 (GI₅₀ = 2.8 µM) cell lines. The most promising of the compounds identified herein were the 4-CF₃ substituted 10 and the 3,4-dichloro substituted 13 with excellent activities against MCF-7 and A431 cell lines. The 3,4-dichloro-13 was a 0.56 µM potent inhibitor of MCF-7 cell growth.]]> Sat 24 Mar 2018 07:59:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19942 Sat 24 Mar 2018 07:58:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19892 Sat 24 Mar 2018 07:57:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19893 Sat 24 Mar 2018 07:57:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17940 Sat 24 Mar 2018 07:56:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20974 Sat 24 Mar 2018 07:54:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5130 Sat 24 Mar 2018 07:48:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28318 50), respectively. Of note, were a CF₃ functionalised anthracenone 4-pyranone (chromone) derivative 22, and an anthracenone-furan derivative 54 which displayed 0.20µM and 0.38µM growth inhibition, respectively, in the BE2-C neuroblastoma cell line.]]> Sat 24 Mar 2018 07:25:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3264 Sat 24 Mar 2018 07:21:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3263 Sat 24 Mar 2018 07:21:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3265 Sat 24 Mar 2018 07:21:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22223 100 μM), as per the parent molecule. We also discovered that the introduction of a terminal phosphate moiety (28) at the same position produced a different trend in cytotoxicity with strong activity in BE2-C (neuroblastoma; GI₅₀ = 9 μM) cells; suggestive of an alternate mode of action.]]> Sat 24 Mar 2018 07:17:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22226 Sat 24 Mar 2018 07:17:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47778 Mon 30 Jan 2023 10:09:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41065 50 values of 0.098, 0.97, 0.13 and 0.21 μM, respectively). Indeed, 6 is 55 times more potent in MDA-MB-468 cells than normal MCF10A breast cells (GI₅₀ of 0.098 vs 5.4 μM) and more than 130 times more potent than in cell lines derived from pancreas, brain and prostate (GI₅₀ of 0.098 vs 10–13 μM). Molecular docking poses of 5 and 6 together with analogue synthesis and phenotypic screening show the importance of the naphthalene moiety, and an ortho-disposed substituent on the N-phenyl moiety for biological activity.]]> Mon 08 Aug 2022 15:04:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40209 Mon 08 Aug 2022 13:40:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42808 Mon 05 Sep 2022 09:57:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42606 Fri 26 Aug 2022 15:48:48 AEST ]]>