@article {LU2019111567,
	title = {Discovery of β-carboline copper(II) complexes as Mcl-1 inhibitor and in~vitro and in~vivo activity in cancer models},
	journal = {Eur. J. Med Chem.},
	volume = {181},
	year = {2019},
	pages = {111567},
	abstract = {<p>Mcl-1 is an anti-apoptotic member of Bcl-2 family proteins. The development of inhibitors of Mcl-1 has been challenging. To develop metal-based Mcl-1inhibitors, twenty two copper(II) complexes 25\&ndash;46 with 9-substituted β-carboline derivatives were reported. Complexes 38 and 39 showed higher cytotoxicity than the corresponding ligands or cisplatin. The most potent complex 39 presented higher selectivity to Mcl-1 than other Bcl-2 family proteins, and killed cancer cells via Bax/Bak mediated apoptosis. Complex 39 showed an excellent safety profile in mouse model, and significantly inhibited the tumor growth in NCI-H460 tumor bearing model, which is more potent than AZD5991 at the same dosage. Complex 39 prolonged the survival time of the tumor bearing mice. Complex 39 is the first metal-based Mcl-1 inhibitor acting as a potential anticancer agent.</p>},
	keywords = {ANTICANCER, apoptosis, COPPER(II) COMPLEX, Mcl-1, β-Carboline},
	issn = {0223-5234},
	doi = {https://doi.org/10.1016/j.ejmech.2019.111567},
	url = {http://www.sciencedirect.com/science/article/pii/S022352341930697X},
	author = {Xing Lu and Yan-Cheng Liu and Chris Orvig and Hong Liang and Zhen-Feng Chen}
}
@article {2650,
	title = {Propofol protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via Akt activation and Bcl-2 up-regulation},
	journal = {Biochemical and Biophysical Research Communications},
	volume = {389},
	number = {1},
	year = {2009},
	note = {ISI Document Delivery No.: 555SMTimes Cited: 4Cited Reference Count: 26Wang, Baohua Shravah, Jayant Luo, Honglin Raedschelders, Koen Chen, David D. Y. Ansley, David M.},
	month = {Nov},
	pages = {105-111},
	type = {Article},
	abstract = {<p>Propofol is a widely used intravenous anesthetic agent with antioxidant properties secondary to its phenol based chemical structure. Treatment with propofol has been found to attenuate oxidative stress and prevent ischemia/reperfusion injury in rat heart. Here, we report that propofol protects cardiac H9c2 cells from hydrogen peroxide (H2O2)-induced injury by triggering the activation of Akt and a parallel up-regulation of Bcl-2. We show that pretreatment with propofol significantly protects against H2O2-induced injury. We further demonstrate that propofol activates the PI3K-Akt signaling pathway. The protective effect of propofol on H2O2-induced injury is reversed by PI3K inhibitor wortmannin, which effectively suppresses propofol-induced activation of Akt, up-regulation of Bcl-2, and protection from apoptosis. Collectively, our results reveal a new mechanism by which propofol inhibits H2O2-induced injury in cardiac H9c2 cells, supporting a potential application of propofol as a preemptive cardioprotectant in clinical settings such as coronary bypass surgery. (C) 2009 Elsevier Inc. All rights reserved.</p>},
	keywords = {15-F-2T-ISOPROSTANE FORMATION, Akt, antioxidant capacity, apoptosis, Bcl-2, CARDIOMYOCYTES, ENDOTHELIAL-CELLS, H9c2 cells, INJURY, KINASE-C, OXIDATIVE STRESS, Propofol, RAT-HEART, REDUCES APOPTOSIS, REPERFUSION, SENSITIVITY, SURVIVAL},
	isbn = {0006-291X},
	doi = {doi: 10.1016/j.bbrc.2009.08.097},
	url = {<Go to ISI>://000274534900020},
	author = {Wang, B. H. and Shravah, J. and Luo, H. L. and Raedschelders, K. and Chen, D. D. Y. and Ansley, D. M.}
}
@article {2350,
	title = {Rationale, design and baseline characteristics of the PROJECT II study: PROpofol CardioproTECTion for Type II diabetics A randomized, controlled trial of high-dose propofol versus isoflurane preconditioning in patients undergoing on-pump coronary artery b},
	journal = {Contemporary Clinical Trials},
	volume = {30},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 456NPTimes Cited: 1Cited Reference Count: 23Ansley, David M. Raedschelders, Koen Chen, David D. Y. Choi, Peter T.},
	month = {Jul},
	pages = {380-385},
	type = {Article},
	abstract = {Diabetes mellitus is a leading cause of death globally and results in significant morbidity and mortality following surgery. After cardiac surgery, diabetic patients are especially at risk for low cardiac output syndrome, which can quadruple the risk for postoperative death. Attempts to prevent low cardiac output syndrome have focused on increasing myocardial tolerance to ischemia (preconditioning), which involves the myocardial mitochondrial ATP-regulated K-ATP channel. G-protein initiation, nitric oxide synthase, and protein kinase C. Unfortunately, the signal transduction pathways required for preconditioning are corrupted in diabetes. Effective antioxidant intervention during ischemia-reperfusion appears important for preserving myocardial function: thus, alleviating oxidant-mediated post-ischemic injury by increasing antioxidant defenses (cardioprotection) is an alternative to preconditioning. Our previous work suggests that propofol(2,6-diisopropylphenol), an intravenous anesthetic with antioxidant potential, may confer cardioprotection. In this paper, we describe the rationale and methodology of the Pro-TECT II Study, a Phase II randomized controlled trial designed to explore the relationships of biomarkers of oxidative or nitrosative stress in diabetes, to determine the effect of propofol cardioprotection to counteract these effects in patients undergoing elective primary coronary bypass graft surgery with cardiopulmonary bypass, and to provide feasibility and sample size data needed to conduct Phase III trials. (C) 2009 Elsevier Inc. All rights reserved.},
	keywords = {15-F-2T-ISOPROSTANE FORMATION, antioxidant, apoptosis, CAPACITY, Cardiopulmonary bypass, Diabetes mellitus, EXPRESSION, F2-isoprostanes, HYPERGLYCEMIA, INJURY, MORTALITY, MYOCARDIAL-INFARCTION, Nitric oxide synthase type III, PREDICTORS, Propofol, SHORT-TERM},
	isbn = {1551-7144},
	url = {<Go to ISI>://000266853900014},
	author = {Ansley, D. M. and Raedschelders, K. and Chen, D. D. Y. and Choi, P. T.}
}
@article {2287,
	title = {Toward [F-18]-labeled aryltrifluoroborate radiotracers: In vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice},
	journal = {Journal of the American Chemical Society},
	volume = {130},
	number = {36},
	year = {2008},
	note = {ISI Document Delivery No.: 344TPTimes Cited: 15Cited Reference Count: 35Ting, Richard Harwig, Curtis auf dem Keller, Ulrich McCormick, Siobhan Austin, Pamela Overall, Christopher M. Adam, Michael J. Ruth, Thomas J. Perrin, David M.},
	month = {Sep},
	pages = {12045-12055},
	type = {Article},
	abstract = {The use of a boronic ester as a captor of aqueous [F-18]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [F-18]-labeled trifluoroborate should be humorally stable such that it neither leaches free [F-18]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [F-18]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [F-18]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [F-18]-PET reagents.},
	keywords = {apoptosis, BIODISTRIBUTION, CANCER, DESIGN, F-18, MICROPET, NO-CARRIER, PEPTIDES, PET, STABILITY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000258950500044},
	author = {Ting, R. and Harwig, C. and auf dem Keller, U. and McCormick, S. and Austin, P. and Overall, C. M. and Adam,Michael J. and Ruth, T. J. and Perrin,David M.}
}
@article {2287,
	title = {Toward [F-18]-labeled aryltrifluoroborate radiotracers: In vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice},
	journal = {Journal of the American Chemical Society},
	volume = {130},
	number = {36},
	year = {2008},
	note = {ISI Document Delivery No.: 344TPTimes Cited: 15Cited Reference Count: 35Ting, Richard Harwig, Curtis auf dem Keller, Ulrich McCormick, Siobhan Austin, Pamela Overall, Christopher M. Adam, Michael J. Ruth, Thomas J. Perrin, David M.},
	month = {Sep},
	pages = {12045-12055},
	type = {Article},
	abstract = {The use of a boronic ester as a captor of aqueous [F-18]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [F-18]-labeled trifluoroborate should be humorally stable such that it neither leaches free [F-18]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [F-18]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [F-18]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [F-18]-PET reagents.},
	keywords = {apoptosis, BIODISTRIBUTION, CANCER, DESIGN, F-18, MICROPET, NO-CARRIER, PEPTIDES, PET, STABILITY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000258950500044},
	author = {Ting, R. and Harwig, C. and auf dem Keller, U. and McCormick, S. and Austin, P. and Overall, C. M. and Adam,Michael J. and Ruth, T. J. and Perrin,David M.}
}
@article {1368,
	title = {Calcium ion exchange in crystalline gelsolin},
	journal = {Journal of Molecular Biology},
	volume = {357},
	number = {3},
	year = {2006},
	note = {ISI Document Delivery No.: 030IYTimes Cited: 6Cited Reference Count: 24},
	month = {Mar},
	pages = {773-782},
	type = {Article},
	abstract = {Gelsolin is a calcium and pH-sensitive modulator of actin filament length. Here, we use X-ray crystallography to examine the extraction and exchange of calcium ions from their binding sites in different crystalline forms of the activated N and C-terminal halves of gelsolin, G1-G3 and G4-G6, respectively. We demonstrate that the combination of calcium and low pH activating conditions do not induce conformational changes in G4-G6 beyond those elicited by calcium alone. EGTA is able to remove calcium ions bound to the type I and type II metal ion-binding sites in G4-G6. Constrained by crystal contacts and stabilized by interdomain interaction surfaces, the gross structure of calcium-depleted G4-G6 remains that of the activated form. However, high-resolution details of changes in the ion-binding sites may represent the initial steps toward restoration of the arrangement of domains found in the calcium-free inactive form of gelsolin in solution. Furthermore, bathing crystals with the trivalent calcium ion mimic, Tb3+, results in anomalous scattering data that permit unequivocal localization of terbium ions in each of the proposed type I and type II ion-binding sites of both halves of gelsolin. In contrast to predictions based on solution studies, we find that no calcium ion is immune to exchange. (c) 2006 Elsevier Ltd. All rights reserved.},
	keywords = {actin, ACTIN MONOMER, ACTIVATION, apoptosis, BINDING-SITE, C-TERMINAL HALF, calcium activation, COMPLEX, CONFORMATIONAL CHANGE, DOMAINS, ELECTRON-DENSITY MAPS, gelsolin, IDENTIFICATION, MECHANISMS, protein crystallography},
	isbn = {0022-2836},
	url = {<Go to ISI>://000236629300008},
	author = {Chumnarnsilpa, S. and Loonchanta, A. and Xue, B. and Choe, H. and Urosev, D. and Wang, H. and Lindberg, U. and Burtnick, L. D. and Robinson, R. C.}
}
@article {1505,
	title = {Identification of sokotrasterol sulfate as a novel proangiogenic steroid},
	journal = {Circulation Research},
	volume = {99},
	number = {3},
	year = {2006},
	note = {ISI Document Delivery No.: 070DTTimes Cited: 3Cited Reference Count: 39Murphy, Siun Larrivee, Bruno Pollet, Ingrid Craig, Kyle S. Williams, David E. Huang, Xin-Hui Abbott, Megan Wong, Fred Curtis, Cameron Conrads, Thomas P. Veenstra, Timothy Puri, Mira Hsiang, York Roberge, Michel Andersen, Raymond J. Karsan, Aly},
	month = {Aug},
	pages = {257-265},
	type = {Article},
	abstract = {The potential to promote neovascularization in ischemic tissues using exogenous agents has become an exciting area of therapeutics. In an attempt to identify novel small molecules with angiogenesis promoting activity, we screened a library of natural products and identified a sulfated steroid, sokotrasterol sulfate, that induces angiogenesis in vitro and in vivo. We show that sokotrasterol sulfate promotes endothelial sprouting in vitro, new blood vessel formation on the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid is critical for promoting angiogenesis, as the desulfated steroid exhibited no endothelial sprouting activity. We thus developed a chemically synthesized sokotrasterol sulfate analog, 2 beta,3 alpha,6 alpha-cholestanetrisulfate, that demonstrated equivalent activity in the hindlimb ischemia model and resulted in the generation of stable vessels that persisted following cessation of therapy. The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity and vascular endothelial growth factor induction, as inhibition of either cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis. Surface expression of alpha(v)beta(3) integrin was also necessary for function, as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding abrogated endothelial sprouting and antiapoptotic activity in response to sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its analogs can promote angiogenesis in vitro and in vivo and could potentially be used for promoting neovascularization to relieve the sequelae of vasoocclusive diseases.},
	keywords = {ACTIVATION, ANGIOGENESIS, apoptosis, ARTERIOGENESIS, ENDOTHELIAL-CELLS, endothelium, IN-VITRO, INHIBITION, INTEGRIN ALPHA(V)BETA(3), ischemia, MARINE NATURAL-PRODUCTS, NF-KAPPA-B},
	isbn = {0009-7330},
	url = {<Go to ISI>://000239501200009},
	author = {Murphy, S. and Larrivee, B. and Pollet, I. and Craig, K. S. and Williams, D. E. and Huang, X. H. and Abbott, M. and Wong, F. and Curtis, C. and Conrads, T. P. and Veenstra, T. and Puri, M. and Hsiang, Y. and Roberge, M. and Andersen, R. J. and Karsan, A.}
}
@article {1010,
	title = {Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {12},
	year = {2004},
	note = {ISI Document Delivery No.: 876VBTimes Cited: 20Cited Reference Count: 62},
	month = {Dec},
	pages = {2063-2070},
	type = {Article},
	abstract = {A novel vanadyl curcumin complex (VO(cur)2) has been synthesized and and its physicochemical properties characterized. Biological characterization included in vitro testing for anti-rheumatic activity in synoviocytes, angiogenesis inhibition in smooth muscle cells and anti-cancer potential in mouse lymphoma cells; as well as in vivo testing for hypoglycemic activity by oral gavage in streptozotocin (STZ)-diabetic rats. VO(cur)2 was more effective as an anti-cancer agent, compared to uncomplexed curcumin or vanadyl ion alone, was more than twice as effective as curcumin alone as an anti-arthritic agent, and was more than four times as effective as curcumin alone in inhibiting smooth muscle cell proliferation. In both acute and chronic screening tests, VO(cur)2 was ineffective as an insulin mimetic agent; however, it also proved to be exceptionally non-toxic, with no evidence of negative symptornatology during a month-long treatment period, at doses up to and including 2.0 mmol kg(-1) day(-1). (C) 2004 Elsevier Inc. All rights reserved.},
	keywords = {antioxidant, apoptosis, arthritis lymphoma, BIS(MALTOLATO)OXOVANADIUM(IV), CELLS, COMPLEX, COORDINATION, curcurnin, DIABETIC-RATS, DIFERULOYL METHANE CURCUMIN, FREE-RADICALS, INDUCED LIPID-PEROXIDATION, INSULIN MIMICS, LEUKEMIA HL-60, METAL-IONS, OXIDATIVE STRESS, vanadyl ion},
	isbn = {0162-0134},
	url = {<Go to ISI>://000225525200010},
	author = {Thompson, K. H. and Bohmerle, K. and Polishchuk, E. and Martins, C. and Toleikis, P. and Tse, J. and Yuen, V. and McNeill, J. H. and Orvig, Chris}
}
@article {813,
	title = {Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF},
	journal = {Embo Journal},
	volume = {23},
	number = {14},
	year = {2004},
	note = {ISI Document Delivery No.: 847NBTimes Cited: 41Cited Reference Count: 59},
	month = {Jul},
	pages = {2713-2722},
	type = {Article},
	abstract = {The actin filament-severing functionality of gelsolin resides in its N-terminal three domains (G1 - G3). We have determined the structure of this fragment in complex with an actin monomer. The structure reveals the dramatic domain rearrangements that activate G1 - G3, which include the replacement of interdomain interactions observed in the inactive, calcium-free protein by new contacts to actin, and by a novel G2 - G3 interface. Together, these conformational changes are critical for actin filament severing, and we suggest that their absence leads to the disease Finnish-type familial amyloidosis. Furthermore, we propose that association with actin drives the calcium-independent activation of isolated G1 G3 during apoptosis, and that a similar mechanism operates to activate native gelsolin at micromolar levels of calcium. This is the first structure of a filament-binding protein bound to actin and it sets stringent, high-resolution limitations on the arrangement of actin protomers within the filament.},
	keywords = {5-BISPHOSPHATE, actin, AMYLOIDOSIS-FINNISH TYPE, apoptosis, BINDING-SITE, CA2+ REGULATION, calcium, CRYSTAL-STRUCTURE, crystallographic structure, F-ACTIN, FAMILIAL AMYLOIDOSIS, FILAMENT BARBED ENDS, gelsolin, PHOSPHATIDYLINOSITOL 4, PLASMA GELSOLIN, X-RAY},
	isbn = {0261-4189},
	url = {<Go to ISI>://000223398800002},
	author = {Burtnick, L. D. and Urosev, D. and Irobi, E. and Narayan, K. and Robinson, R. C.}
}
@article {5130,
	title = {Arsenicals inhibit thioredoxin reductase in cultured rat hepatocytes},
	journal = {Chemical Research in Toxicology},
	volume = {14},
	number = {3},
	year = {2001},
	note = {ISI Document Delivery No.: 415LTTimes Cited: 86Cited Reference Count: 46},
	month = {Mar},
	pages = {305-311},
	type = {Article},
	abstract = {Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAsIII), are potent noncompetitive inhibitors of TR purified from mouse liver. Because MAsIII is produced in the biomethylation of As, it was postulated that the extent of inhibition of TR in cultured rat hepatocytes would correlate with the intracellular concentration of methyl As. Exposure of cultured hepatocytes to inorganic As-III (iAs(III)), MAsIII, or aurothioglucose (ATG, a competitive inhibitor of TR activity) for 30 min caused a concentration-dependent reduction in TR activity. The estimated IC50 was much greater than 100 muM for iAS(III), similar to 10 muM for ATG, and similar to3 muM for MAsIII. In hepatocytes exposed to 1 muM MAsIII for up to 24 h, the inhibition of TR activity was maximal (similar to 40\%) after exposure for 15 min. After exposure for 3 h [when most MAsIII has been converted to dimethyl As (DMAs)], TR activity in these cells had returned to control levels. Notably, exposure of the cell to 50 muM DMAsIII did not affect TR activity. In hepatocytes exposed to 10 muM iAs(III) for up to 24 h, the inhibition of TR activity was progressive; at 24 h, activity was reduced similar to 35\%. Following exposure to iAsIII or MAsIII, the extent of inhibition of TR activity correlated strongly with the intracellular concentration of MAs. Taken together, these results suggest that arsenicals formed in the course of cellular metabolism of As are potent inhibitors of TR activity. In particular, MAsIII, an intermediate in the metabolic pathway, is an especially potent inhibitor of TR. Hence, the capacity of cells to produce or consume the intermediates in the pathway for As methylation may be an important determinant of susceptibility to the toxic effects of As.},
	keywords = {apoptosis, ENZYMATIC REDUCTION, IN-VITRO METHYLATION, LIVER, MAMMALIAN SYSTEMS, MONOMETHYLARSONOUS ACID MMA(III), NF-KAPPA-B, RABBIT ERYTHROCYTES, REDOX, REGULATION, SUBSTRATE},
	isbn = {0893-228X},
	url = {<Go to ISI>://000167723600007},
	author = {Lin, S. and Del Razo, L. M. and Styblo, M. and Wang, C. Q. and Cullen, W. R. and Thomas, D. J.}
}
