https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44078 6] and the protic ionic liquid ethanolammonium nitrate (ETAN) failed. Microwave irradiation in EAN facilitated rapid access to three focused libraries, based on the parent isocyanide: cyclohexyl isocyanide, benzyl isocyanide and ethyl isocyanoacetate. Analysis of the structure activity relationship data suggested the presence of a bulky moiety originating from the isocyanide (cyclohexyl and benzyl) enhanced cytotoxicity. Removal of the acetylenic H-atom from the ethanoic acid moiety was detrimental to cytotoxicity. The most active analogues produced, N-(2-cyclohexylamino)-1-(4-methoxyphenyl)-2-oxoethyl-N-(3,5-dimethoxyphenyl)propiolamide, returned average GI₅₀ values of ≤1 μM across the cancer cell lines evaluated. Combined, these data suggest that analogues of this nature are interesting potential anti-cancer development leads.]]> Wed 26 Oct 2022 10:31:27 AEDT ]]> 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:37074 Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines. The antibacterial activity was assessed using the disc diffusion method and minimum inhibitory concentration (MIC) values were determined. The results revealed that the saponin-enriched fractions from H. hirsuta leaves and stems showed the highest antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL, respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL, respectively). Importantly, these saponin-enriched fractions possessed strong anticancer activity in vitro towards a range of cancer cell lines including MIA PaCa-2 (pancreas); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate); HT29 (colon); MCF-7 (breast); SJ-G2, U87, SMA (glioblastoma) and BE2-C (neuroblastoma) at low doses (GI₅₀ values of 0.36–11.17 µg/mL). They especially revealed potent anti-pancreatic cancer activity in vitro against MIA PaCa-2, BxPC-3 and CFPAC-1 cells with IC50 values of 1.80–6.43 µg/mL. This finding provides scientific evidence of the cytotoxic activity of the extracts prepared from H. hirsuta leaves and stems, and suggests further studies to isolate active compounds for development of new anticancer agents from these plant extracts.]]> Wed 19 Jan 2022 15:15:13 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:19242 Wed 11 Apr 2018 12:53:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30063 50 μM across all cell lines, with the 2-OH-Ph substituted 12l analogue presenting with sub-micromolar potency against the A2780 (ovarian; 0.34 ± 0.04 μM), BEC-2 (glioblastoma; 0.35 ± 0.06 μM), MIA (pancreas; 0.91 ± 0.054 μM) and SMA (murine glioblastoma; 0.77 ± 0.029 μM) carcinoma cell lines. Interestingly, the U87 glioblastoma cell line showed inherent resistance to growth inhibition by all analogues (GI50 32 to >50 μM) while the A2780 cells were highly sensitive (GI50 3.8–0.34 μM), suggesting that the analogues developed herein may be valuable lead compounds for the development of ovarian carcinoma specific cytotoxic agents. The differences in amide versus ester cytotoxicity was consitent with esterase cleaveage to release the cytotoxic warhead.]]> Wed 11 Apr 2018 11:15:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28064 Wed 11 Apr 2018 09:24:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36554 Catharanthus roseus (L.) G. Don (C. roseus) stem. C. roseus stem was powdered and extracted with methanol using ultrasound-assisted extraction to obtain the crude extract. The crude extract was further fractioned using liquid-liquid extraction technique to obtain extracts of increasing polarity including n-butanol and residual aqueous fractions. The crude extract and its derived fractions were then subjected to phytochemical screening and assayed for antioxidant, antimicrobial and cytotoxic activities. Results showed that the n-butanol fraction contained the highest levels of saponins and phenolics (3037.54 mg ESE/g and 77.87 mg GAE/g, respectively) and possessed the strongest antioxidant capacity amongst the tested extracts. HPLC analysis revealed that this n-butanol fraction had high levels of apigenin and kaempferol, whereas the aqueous fraction contained a high level of gallic acid. The n-butanol fraction was found to effectively inhibit the activity of Escherichia coli and Staphylococccus lugdunensis. The n-butanol fraction also possessed strong cytotoxic activity in vitro against a wide range of cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma) at low doses (GI50 values of 5.2−21.0 µg/mL). These results indicate that the n-butanol fraction prepared from C. roseus stem is a rich source of bioactive compounds which can be isolated for further evaluation as potential antimicrobial drugs or antitumor therapeutic agents.]]> Wed 09 Mar 2022 16:00:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34765 1H, ¹³C, ¹¹⁹Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph₂SnCl₂ or Me₂SnCl₂ with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R2Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me₂Sn(S2MoVa), Me₂Sn(S4MoVa) and Me₂Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C2NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.]]> Wed 09 Feb 2022 15:52:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43936 Wed 05 Oct 2022 12:44:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48769 Wed 05 Apr 2023 14:02:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48768 Wed 05 Apr 2023 13:55:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34052 Escherichia coli and Gram-positive Bacillus subtilis species, these analogues showed up to 100% growth inhibition at 200 μM. 2-((Z)-4-(((Z)-4-(4-((E)-(Carbamimidoylimino)methyl)phenoxy)but-2-en-1-yl)oxy)benzylidene)hydrazine-1-carboximidamide 22 showed excellent activity against important pathogens. With minimum inhibitory concentration values of ≤3 μg/mL for Gram-positive Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus and ≤51 μg/mL for Gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, 22 is a potent lead for a novel antibacterial target. Epifluorescence studies in live bacteria were consistent with 22, inhibiting the NusB–NusE PPI as proposed.]]> Wed 04 Sep 2019 09:54:32 AEST ]]> 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:54455 Tue 27 Feb 2024 13:53:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20160 36-fold reduced activity against rings, suggesting that they can discriminate between helical or ring oligomerization states. 4a and 6a inhibited dynamin-dependent endocytosis of transferrin in multiple cell types (IC50 of 5.7 and 5.8 μM, respectively), at least sixfold more potently than dynasore, but had no effect on dynamin-independent endocytosis of cholera toxin. 4a also reduced synaptic vesicle endocytosis and activity-dependent bulk endocytosis in cultured neurons and synaptosomes. Overall, 4a and 6a are improved and versatile helical dynamin and endocytosis inhibitors in terms of potency, non-specific binding and cytotoxicity. The data further suggest that the ring oligomerization state of dynamin is not required for clathrin-mediated endocytosis.]]> Tue 24 Aug 2021 14:23:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31507 Phyllanthus amarus (P. amarus) has been used as a medicinal plant for the prevention and treatment of chronic ailments such as diabetes, hepatitis, and cancer. Methods: The physicochemical properties, antioxidant and cytotoxic activities of crude extracts and fractions from P. amarus were determined using spectrophotometric method. Results: The P. amarus methanol (PAM) extract had lower levels of residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids, and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents per g dried extract, respectively) than those of the P. amarus water (PAW) extract. The antioxidant activity of PAM extract was significantly higher (p < 0.05) than that of the PAW extract, PAM fractions, and phyllanthin (known as a major compound in the P. amarus). Higher cytotoxic activity of PAM extract based on MTT assay on different cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed in comparison to the PAW extract and PAM fractions. The cytotoxic potential of the PAW extract (200 µg/mL), based on the CCK-8 assay on a pancreatic cancer cell line (MiaCaPa2) was significantly lower (p < 0.05) than those of gemcitabine (50 nM) and a saponin-enriched extract from quillajia bark at 200 µg/mL (a commercial product), but was significantly higher than that of phyllanthin at 2 µg/mL. Conclusions: The results achieved from this study reveal that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs.]]> Tue 17 Mar 2020 11:32:49 AEDT ]]> 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:33062 Paramignya trimera (Oliv.) Guillaum) has been used as a medicinal plant for cancer prevention and treatment in recent years. The objective of this study was to determine the physicochemical, antioxidant, and cytotoxic properties of crude P. trimera root (PTR) extract and its fractions using MeOH as a solvent and microwave‐assisted extraction as an advanced technique for preparation of the PTR extract. The results showed that the PTR extract had high contents of saponins, phenolics, flavonoids, and proanthocyanidins (7731.05 mg escin equiv. (EE), 238.13 mg gallic acid equiv. (GAE), 81.49 mg rutin equiv., and 58.08 mg catechin equiv. (CE)/g dried extract, resp.). Antioxidant activity of PTR extract was significantly higher (P < 0.05) than those of four its fractions and ostruthin, a key bioactive compound in the P. trimera, while potent cytotoxic capacity of PTR extract on various cancer cell lines in terms of MiaPaCa‐2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2‐C (neuroblastoma), MCF‐7 (breast), MCF‐10A (normal breast), and U87, SJ‐G2, SMA (glioblastoma) was observed with GI₅₀ values ranging from 15 to 32 μg/ml. Cytotoxic potential on pancreatic cancer cells of PTR extract (100 – 200 μg/ml) was significantly higher (P < 0.05) than those of its four fractions (50 μg/ml), ostruthin (20 μg/ml) and gemcitabine (50 nm), and being comparable to a saponin‐enriched extract from quillajia bark, a commercial product. Based on the results achieved, we can conclude that the PTR extract is a potential source for application of in the nutraceutical, medical, and pharmaceutical industries.]]> Thu 17 Feb 2022 09:31:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33061 Paramignya trimera) has been used for the treatment of cancer and cancer‐like aliments. Among different parts of the P. trimera plant, leaf is considered as a residual part after harvesting of the root. This study aimed to determine the physiochemical properties and the antioxidant and anti‐proliferative capacities of P. trimera leaf (PTL) using microwave drying for the preparation of dry sample; MeOH and microwave‐assisted extraction for the preparation of crude extract; and freeze‐drying for the preparation of powdered extract. The results showed that total phenolic, total flavonoid, proanthocyanidin, and saponin contents of PTL prepared by microwave drying at 450 W were 25.4 mg gallic acid equiv. (GAE), 86.3 mg rutin equiv. (RE), 5.6 mg catechin equiv. (CE), and 702.1 mg escin equiv. (EE) per gram dried sample, respectively. Gallic acid, protocatechuic acid, ellagic acid, rutin, and quercetin were identified in the PTL MeOH extract. Dried PTL displayed potent antioxidant activity, while the powdered PTL extract exhibited great anti‐proliferative capacity on various cancer cell lines including MiaPaCa‐2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2‐C (neuroblastoma), MCF‐7 (breast), MCF‐10A (normal breast), and U87, SJ‐G2, and SMA (glioblastoma). Anti‐proliferative capacity on pancreatic cancer cells (MiaCaPa2, BxPc3, and CFPAC1) of PTL extract (200 μg/ml) was significantly higher (P < 0.05) than those of ostruthin (20 μg/ml) and gemcitabine (50 nm), and to be comparable to the powdered P. trimera root extract and a saponin‐enriched extract from quillajia bark (a commercial product). The findings from this study allow us to conclude that the PTL is a rich source of phytochemicals that possess promising antioxidant and anti‐proliferative activities, therefore it shows potential as lead compounds for application in the nutraceutical, medicinal and pharmaceutical industries.]]> Thu 17 Feb 2022 09:31:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36553 Catharanthus roseus (L.) G. Don (C. roseus) is a well-known medicinal plant for its source of alkaloids solely found in the leaves. Other parts including the root are usually discarded after the alkaloid extraction. This study sought to investigate phytochemical profiles, antioxidant, antimicrobial and cytotoxic properties of the C. roseus root extract (RE) and its two sub-fractions including saponin-enriched (SE) and aqueous (AQ) fractions. The results showed that the RE was a rich source of saponins (1744.44 mg ESE/g) and phenolics (51.27 mg GAE/g), which comprised of gallic acid (25.74 mg/g), apigenin (1.45 mg/g) and kaempferol (1.58 mg/g). The SE fraction was enriched with 31% of saponins and 63% of phenolics higher than those of the RE; whereas the concentrations of saponins and phenolics of the AQ fraction were lower than those of the RE by 40% and 74%, respectively. The content of gallic acid in the SE fraction was 1.4-fold and 1.5-fold higher than those of the RE or AQ fraction, respectively. The SE fraction demonstrated potent antioxidant capacity, which was significantly higher than the RE or AQ fraction, and also exhibited strong anti-proliferative activity against 11 cancer cell lines including A2780 (ovarian), H460 (lung), A431 (skin), MIA PaCa-2 (pancreas), Du145 (prostate), HT29 (colon), MCF-7 (breast), BE2-C (neuroblastoma), SJ-G2, U87 and SMA (glioblastoma) with low GI₅₀ values (≤ 2.00 µg/mL). The SE fraction was also shown to effectively inhibit the growth of both bacteria (Escherichia coli, Enterobacter aerogenes and Staphylococccus lugdunensis) and fungi (Candida albicans and Aspergillus niger). These findings warrant further investigation to isolate major compounds from the SE fraction and further test their antioxidant, anticancer and antimicrobial activities.]]> Thu 17 Feb 2022 09:27:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50836 Thu 17 Aug 2023 11:57:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48035  47 (3-Cl) > 46 (2-Cl)) against the cell lines examined. The introduction of bulky aromatic moieties was well tolerated, e.g. dihydrobenzo[b][1,4]dioxine (51) returned cohort-2 GI50 values of 1.2-3.4 μM. In all instances the observed docked binding poses and binding scores were consistent with the observed cytotoxicity. This in turn supports, but does not prove, that these analogues function via S100A2-p53 binding groove inhibition.]]> Thu 16 Feb 2023 11:04:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29794 Thu 04 Nov 2021 10:39:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32119 (CME) = 65.9 ± 7.7 to 3.7 ± 1.1 mM), which makes this series among the more potent inhibitors of dynamin and CME yet reported. In CME and growth inhibition cell-based assays, the data obtained was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-target effects at the cholecystokinin, dopamine D₂, histamine H₁ and H₂, melanocortin, melatonin, muscarinic M₁ and M₃, neurokinin, opioid KOP and serotonin receptors.]]> Thu 03 May 2018 12:18:53 AEST ]]> 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:8338 Sat 24 Mar 2018 08:37:03 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:1259 Sat 24 Mar 2018 08:32:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:2497 1.1, additivity by a CI between 0.9 and 1.1, and synergism by a CI<0.9. Results: Both cell lines were equally sensitive to cantharidin alone (GI50 values 5.4 and 7.3 mgrM), which induced a significant increase in the S-phase population of both cell lines within 6 h with a concomitant increase in DNA synthesis. This response culminated in G2/M cell cycle arrest within 24 h and subsequent cell death. In response to nolatrexed alone, HT29 cells were more sensitive than HCT116 cells (GI50 1.9 mgrM vs 9.8 mgrM), with G1/S-phase cell cycle arrest occurring within 24 h in both cell lines. In HT29 cells, this was followed by cell death, whereas in HCT116 cells, a proportion of cells died following arrest but the predominant event was re-entry into the cell cycle. The simultaneous exposure of HT29 cells to the combination of nolatrexed and cantharidin in drug molar ratios of 1:1 and 1:2.5 for 72 h was synergistic producing composite CIs of 0.88 and 0.87, respectively. The sequence of nolatrexed followed by cantharidin 24 h later resulted in greater synergism (CI values of 0.75, 0.52, 0.55, 0.68 for molar ratios of 10:1, 1:1, 1:2.5, 1:10), whereas the reverse sequence was antagonistic, suggesting that the point of interaction is downstream of TS inhibition. In HCT116 cells only additive and antagonistic interactions were observed for any of the treatment combinations. The lack of synergism in these cells may be caused by the reduced sensitivity of these cells to nolatrexed as a single agent. Conclusion: The effect of TS inhibition can be enhanced by the inhibition of serine/threonine protein phosphatases.]]> Sat 24 Mar 2018 08:27:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1773 1000 μM. Analogues possessing good PP1 and/or PP2A inhibition also returned moderate to good anti-cancer activity. Analogues with substituents directly attached to the intact bicyclo[2.2.1]heptane skeleton were poor to moderate anti-cancer agents. This correlates well with their lack of PP1 or PP2A activity. Analogues capable of undergoing a facile ring opening of the anhydride or with a single carboxylate were good PP1 and PP2A inhibitors, largely correlating to the observed anti-cancer activity in all cases, except 11. Analogue 11, whist neither a PP1 nor a PP2A inhibitor shows anti-cancer activity comparable to 1 and 2. We believe that intracellular esterases generate the corresponding dicarboxylate, which is a potent PP1 and PP2A inhibitor, and that it is this species which is responsible for the observed anti-cancer activity.]]> Sat 24 Mar 2018 08:27:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1723 Sat 24 Mar 2018 08:27:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12336 Sat 24 Mar 2018 08:15:52 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: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:19893 Sat 24 Mar 2018 07:57:02 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: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:18787 50) of 42 μM in MCF-7 (breast) cells and 24 μM in A2780 (ovarian) cells and >50 μM in all other cell lines tested. The development of eight focused libraries comprising thirty compounds total identified N-(biphenyl-4-ylmethyl)-1H-pyrrole-2-carboxamide (4l), N-benzyl-4,5-dibromo-1H-pyrrole-2-carboxamide (5a) and N-(biphenyl-4-ylmethyl)-4,5-dibromo-1H-pyrrole-2-carboxamide (5l) as potent inhibitors of cell growth in our panel of cell lines. Of these compounds GI₅₀ values of <5 μM were observed with 4l against HT29 (colon) and SW480 (colon); 5a against HT29; and 5l against HT29, SW480, MCF-7, A431 (skin), Du145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas) cell lines. As a cancer class, colon cancer appears to be more sensitive to the oroidin series of compounds, with analogue 5l being the most active.]]> Sat 24 Mar 2018 07:51:02 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:5432 Sat 24 Mar 2018 07:48:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27329 Eucalyptus robusta (Sm.) (ER) is a widely distributed tree native to the east coast of Australia, which has also been established in numerous other countries. ER leaves contain high levels of essential oils and are rich in total phenolic compounds (TPC), which have been linked with health benefits; however, there is limited information on the bioactivity of ER leaf extracts. This study aimed to optimise water extraction conditions for TPC, prepare a spray-dried powdered extract and test its physicochemical, antioxidant and anti-proliferative properties. The results showed that optimal water extraction conditions for TPC were 85°C, 15 min and a water-to-leaf ratio of 20:1 mL/g. Under these conditions, spray-dried powdered extract was prepared with a recovery yield of 85%. The extract was water-soluble and had a TPC level of 407 mg GAE/g. It also possessed potent antioxidant capacity, comparable to pure ascorbic acid, but higher than pure α-tocopherol. In addition, the powdered extract demonstrated significant activity against a panel of cancer cell lines, which included cancers of the pancreas, breast, lung, brain, skin, colon and ovary. Of note, the ER extract exerted a more significant toxic effect on pancreatic cancer (PC) cells compared to gemcitabine, the first line chemotherapeutic agent for PC. We suggest that future studies should purify individual bioactive compounds from ER for further investigation of its potential health promoting and anti-cancer activity.]]> Sat 24 Mar 2018 07:38:37 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:3324 40- and >30-fold selectivity) over PP2A. Both compounds exhibited moderate PP1 activity, 3 IC₅₀ 50 μM and 6 IC₅₀ 12.5 μM. Interestingly, the corresponding mono-ester derivatives of 3 showed no such selectivity.]]> Sat 24 Mar 2018 07:23:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3327 Sat 24 Mar 2018 07:23:19 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:3185 Sat 24 Mar 2018 07:18:09 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:46611 Mon 28 Nov 2022 10:36:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44187 Mon 10 Oct 2022 10:55:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44154 2Sn(Lⁿ)] and [Sn(Lⁿ)₂] (where R = Ph or Me; Lⁿ = 1, 2, 3 and 4) were synthesized and characterized by elemental analysis, IR, UV–vis, mass spectrometry and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy. X-ray crystallographic data was obtained for 11′, a 2:1 co-crystal between Ph₂Sn(L²) (11) and 3-methoxysalicylaldehyde azine, and Me₂Sn(L²) (12) where L²H₂ is 2-(2-hydroxy-3-methoxybenzylidene)-N-phenylhydrazinecarbothioamide. The analysis revealed distinct coordination geometries for 11 and 12 approaching trigonal–bipyramidal. In the crystal of 11′, supramolecular dimers arising from aminesingle bondNsingle bondH…S(thiolate) hydrogen bonding and {…HNCS}₂ synthons are evident; π(chelate ring)…π(oxidobenzylidene) stacking is also apparent. In the crystal of 12, supramolecular, helical chains are generated by a combination of aminesingle bondNsingle bondH…O(phenoxide) hydrogen bonding and Sn…S secondary bonding. The cytotoxic activity of the compounds against a panel of ten cancer cell lines, [HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast), A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas), and one normal cell line, MCF-10A (normal breast)] were investigated. The thiosemicarbazone Schiff bases 1 and 4 as well as the diphenyltin(IV) compounds showed a strong ability to inhibit the growth of cancer cells, with particular selectivity against HT29, MCF-7, A2780, A431, BE2-C, SJ-G2 and MIA cell lines. The structure–activity relationship of all these compounds were studied by evaluating the effect of alkyl and aryl groups attached on the thiosemicarbazone backbone, the methoxy/hydroxyl groups present at the meta-position of the phenyl ring and alkyl or aryl groups bound to the tin center.]]> Mon 10 Oct 2022 09:31:33 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40152 2L1, H₂L2 and H₂L3) and 2,3-dihydroxybenzaldehyde (H₂L4, H₂L5 and H₂L6) (where H₂Ln = di-acids of Schiff base) are reported. The compounds were characterised by elemental analysis, FT-IR and multinuclear NMR (¹H, ¹³C and ¹¹⁹Sn) spectroscopy. The crystal structures of tin(IV) [S-4-methybenzyl-β-N-(2-hydroxy-3-methoxybenzylmethylene)dithiocarbazate] (2) and tin(IV) [S-benzyl-β-N-(2-hydroxy-3-methoxy benzylmethylene)dithiocarbazate] (3) were determined by X-ray single crystal diffraction analysis. X-ray crystallography showed the molecular geometries in homoleptic 2 and 3 to be quite similar in which the dinegative tridentate ligand coordinated the tin atoms via thiolate-S, phenoxide-O and imine-N atoms. The coordination geometries are based on an octahedron with like-atoms mutually trans. The experimental findings were validated by density functional theory (DFT) calculations at the B3LYP/LanL2DZ/6-311G(d,p) level of theory. All the tin(IV) compounds, except the insoluble compound 2 were screened for their in vitro cytotoxicity against a panel ten of cancer cell lines and one normal breast cell line (MCF-10 A) by MTT assay. Interestingly, the cytotoxicity of five tin(IV) compounds against HT29, MCF7 and MIA was higher than the reference drug, cisplatin.]]> Fri 15 Jul 2022 09:53:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51500 Fri 08 Sep 2023 11:56:25 AEST ]]>