Chemistry Commons^™

Periplasmic Binding Proteins In Thermophiles: Characterization And Potential Application Of An Arginine-Binding Protein From Thermotoga Maritima: A Brief Thermo-Story, Alessio Ausili, Maria Staiano, Jonathan D. Dattelbaum, Antonio Varriale, Alessandro Capo, Sabato D'Auria

Chemistry Faculty Publications

Arginine-binding protein from the extremophile Thermotoga maritima is a 27.7 kDa protein possessing the typical two-domain structure of the periplasmic binding proteins family. The protein is characterized by a very high specificity and affinity to bind to arginine, also at high temperatures. Due to its features, this protein could be taken into account as a potential candidate for the design of a biosensor for arginine. It is important to investigate the stability of proteins when they are used for biotechnological applications. In this article, we review the structural and functional features of an arginine-binding protein from the extremophile Thermotoga maritima …

Structurally Diverse Hamigerans From The New Zealand Marine Sponge Hamigera Tarangaensis: Nmr-Directed Isolation, Structure Elucidation And Antifungal Activity, A. Jonathan Singh, Jonathan D. Dattelbaum, Jessica J. Field, Zlatka Smart, Ethan F. Woolly, Jacqueline M. Barber, Rosemary Heathcott, John H. Miller, Peter T. Northcote

Chemistry Faculty Publications

The NMR-directed investigation of the New Zealand marine sponge Hamigera tarangaensis has afforded ten new compounds of the hamigeran family, and a new 13-epi-verrucosane congener. Notably, hamigeran F (6) possesses an unusual carbon–carbon bond between C-12 and C-13, creating an unprecedented skeleton within this class. In particular, the structural features of 6, hamigeran H (10) and hamigeran J (12) imply a diterpenoid origin, which has allowed the putative biogenesis of three hamigeran carbon skeletons to be proposed based on geranyl geranyl pyrophosphate. All new hamigerans exhibited micromolar activity towards the HL-60 …

Theoretical Design Of Stable Small Aluminium-Magnesium Binary Clusters, Edison Osorio, Alejandro Vasquez, Elizabeth Florez, Fanor Mondragon, Kelling J. Donald, William Tiznado

Chemistry Faculty Publications

We explore in detail the potential energy surfaces of the Al_xMg_y (x, y = 1–4) systems as case studies to test the utility and limitations of simple rules based on electron counts and the phenomenological shell model (PSM) for bimetallic clusters. We find that it is feasible to design stable structures that are members of this set of small Al–Mg binary clusters, using simple electron count rules, including the classical 4n + 2 Hückel model, and the most recently proposed PSM. The thermodynamic stability of the title compounds has been evaluated using several different descriptors, including …

Oxidative Modification Of Lipoic Acid By Hne In Alzheimer Disease Brain, Sarita S. Hardas, Rukhsana Sultana, Amy M. Clark, Tina L. Beckett, Luke I. Szweda, M. Paul Murphy, D. Allan Butterfield

Chemistry Faculty Publications

Alzheimer disease (AD) is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP) and intracellular neurofibrillary tangles (NFTs). The major component of SP is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid …

Host–Guest Complexes Of Pentiptycene Receptors Display Edge-To-Face Interaction, Lorenzo Mosca, Petr Koutník, Vincent M. Lynch, Grigory V. Zyryanov, Nina A. Esipenko, Pavel Anzenbacher Jr.

Chemistry Faculty Publications

The pentiptycene receptors form edge-to-face complexes with a variety of aromatic guests including nitroaromatics. X-ray diffractometry revealed that compounds 1, 2, and 3 form host-guest assemblies with a thienyl fragment (from a neightboring molecule of 1), benzene and nitrobenzene, respectively. X-ray studies of the three crystal structures reported here strongly suggest the edge-to-face to be a predominant binding mode between the aromatic guests and electron-rich faces of the pentiptycene aromatic cavity.

Supramolecular Sensor For Cancer-Associated Nitrosamines, Tsuyoshi Minami, Nina A. Esipenko, Ben Zhang, Maria E. Kozelkova, Lyle Isaacs, Ryuhei Nishiyabu, Yuji Kubo, Pavel Anzenbacher Jr.

Chemistry Faculty Publications

A supramolecular assay based on two fluorescent cucurbit[n]uril probes enables the recognition and quantification of nitrosamines, including cancer-associated nitrosamines, compounds that are difficult to recognize. The cross-reactive sensor leverages weak interactions and competition among the probe, metal, and guest, yielding high information density in the signal output (variance) and enabling the recognition of structurally similar guests.

Lack Of P53 Affects The Expression Of Several Brain Mitochondrial Proteins: Insights From Proteomics Into Important Pathways Regulated By P53, Ada Fiorini, Rukhsana Sultana, Eugenio Barone, Giovanna Cenini, Marzia Perluigi, Cesare Mancuso, Jian Cai, Jon B. Klein, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

The tumor suppressor protein p53 has been described "as the guardian of the genome" for its crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, senescence, or apoptosis in response to various stress signals. Although p53 promotes longevity by decreasing the risk of cancer through activation of apoptosis or cellular senescence, several findings suggest that an increase of its activity may have deleterious effects leading to selected aspects of the aging phenotype and neurodegenerative diseases. There is the link between p53 and oxidative stress, the latter a crucial factor that contributes to neurodegenerative processes like …

Dynamic Electron Correlation Effects On The Ground State Potential Energy Surface Of A Retinal Chromophore Model, Samer Gozem, Mark Huntress, Igor Schapiro, Roland Lindh, Alexander A. Granovsky, Celestino Angeli, Massimo Olivucci

Chemistry Faculty Publications

The ground state potential energy surface of the retinal chromophore of visual pigments (e.g., bovine rhodopsin) features a low-lying conical intersection surrounded by regions with variable charge transfer and diradical electronic structures. This implies that dynamic electron correlation may have a large effect on the shape of the force fields driving its reactivity. To investigate this effect, we focus on mapping the potential energy for three paths located along the ground state CASSCF potential energy surface of the penta-2,4-dieniminium cation taken as a minimal model of the retinal chromophore. The first path spans the bond length alternation coordinate and intercepts …

Organics In Environmental Ices: Sources, Chemistry, And Impacts, V. F. Mcneill, A. M. Grannas, J. P. D. Abbatt, M. Ammann, P. Ariya, T. Bartels-Rausch, F. Domine, D. J. Donaldson, Marcelo I. Guzman, D. Heger, T. F. Kahan, P. Klán, S. Masclin, C. Toubin, D. Voisin

Chemistry Faculty Publications

The physical, chemical, and biological processes involving organics in ice in the environment impact a number of atmospheric and biogeochemical cycles. Organic material in snow or ice may be biological in origin, deposited from aerosols or atmospheric gases, or formed chemically in situ. In this manuscript, we review the current state of knowledge regarding the sources, properties, and chemistry of organic materials in environmental ices. Several outstanding questions remain to be resolved and fundamental data gathered before an accurate model of transformations and transport of organic species in the cryosphere will be possible. For example, more information is needed regarding …

One-Pot Synthesis Of (Z)-B-Sulfonyl Enoates From Ethyl Propiolate, C. Wade Downey, Smaranda Craciun, Ana M. Neferu, Christina A. Vivelo, Carly J. Mueller, Brian C. Southall, Stephanie Corsi, Eric W. Etchill, Ryan J. Sault

Chemistry Faculty Publications

B-Sulfonyl enoates may be synthesized through a one-pot two-step sequence from ethyl propiolate with good to excellent selectivity for the Z isomer. Trialkylamines catalyze thioconjugate additions of aryl thiols, and alkoxides catalyze the addition of aliphatic thiols. Addition of meta-chloroperbenzoic acid (mCPBA) and LiClO₄ to the reaction mixture provides rapid access to the sulfonyl enoates. Yields of the pure Z isomer range from 51 – 90%.

One-Pot Three-Step Thioconjugate Addition-Oxidation-Diels–Alder Reactions Of Ethyl Propiolate, C. Wade Downey, Smaranda Craciun, Christina A. Vivelo, Ana M. Neferu, Carly J. Mueller, Stephanie Corsi

Chemistry Faculty Publications

Ethyl propiolate undergoes one-pot three-step thioconjugate addition-oxidation-Diels–Alder cycloaddition when treated with a variety of thiols in the presence of catalytic base, meta-chloroperbenzoic acid, lithium perchlorate, and cyclopentadiene. The reaction of S‑aryl thiols is catalyzed by trialkylamines, and the reaction of aliphatic thiols requires catalytic alkoxide base. Yields of the major diastereomer of the conveniently functionalized bicyclic products range from 47 to 81% depending upon the thiol reactant, which compares favorably to yields observed when the entire synthesis is performed step by step.

The Association Of Elevated 2′,5′-Oligoadenylate-Dependent Rnase L With Lung Cancer Correlated With Deficient Enzymatic Activity And Decreased Capacity Of Rnase L Dimerization, Huijing Yin, Aimin Zhou, Yalei Dai

Chemistry Faculty Publications

RNase L mediates critical cellular functions including antiviral, proapoptotic, antiproliferative and tumor suppressive activities. In this study, the expression and function of RNase L in lung cancer cells were examined. Interestingly we have found that the expression of RNase L in lung cancer cells was 3- and 9-fold higher in its mRNA and protein levels, but a significant decrease of its enzymatic activity when compared to that in corresponding normal lung cells. Further investigation revealed that 2-5A-induced dimerization of the RNase L protein, a necessary prerequisite for activation of RNase L, was inhibited, as a result of that RLI, a …

Cox Inhibitors Indomethacin And Sulindac Derivatives As Antiproliferative Agents: Synthesis, Biological Evaluation, And Mechanism Investigation, Snigdha Chennamaneni, Bo Zhong, Rati Lama, Bin Su

Chemistry Faculty Publications

Cyclooxygenase (COX) inhibitors Indomethacin and its structural analogs Sulindac exhibit cell growth inhibition and apoptosis inducing activities in various cancer cell lines via COX independent mechanisms. In this study, the molecular structures of Indomethacin and Sulindac were used as starting scaffolds to design novel analogs and their effects on the proliferation of human cancer cells were evaluated. Compared to Indomethacin and Sulindac inhibiting cancer cell proliferation with IC50s of more than 1 mM, the derivatives displayed significantly increased activities. Especially, one of the Indomethacin analogs inhibited the growth of a series of cancer cell lines with IC50s around 0.5 μM–3 …

Liposome Encapsulation Of A Photochemical No Precursor For Controlled Nitric Oxide Release And Simultaneous Fluorescence Imaging, Alexis D. Ostrowski, Brian F. Lin, Matthew V. Tirrell, Peter C. Ford

Chemistry Faculty Publications

Described are photochemical studies of the nitric oxide precursors, trans-Cr(L)(ONO)(2)(+) (L = cyclam = 1,4,8,11-tetraazacyclotetradecane, CrONO, or L = mac = 5,7-dimethyl-6-anthracenylcyclam, mac-CrONO) encapsulated in phosphatidylcholine liposomes. The liposomes provide a means to maintain a localized high concentration of NO releasing complexes and are easily modified for in vivo targeting through self-assembly. Steady, controlled release of NO is seen after photolysis of the liposome-encapsulated CrONO as compared to the burst of NO release seen by the unencapsulated complex in oxygenated solutions. The quantum yields for photochemical NO release from liposome-encapsulated CrONO and mac-CrONO were determined in both oxygenated and anoxic …

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …

Exploring The Role Of A Conserved Class A Residue In The Ω-Loop Of Kpc-2 Β-Lactamase: A Mechanism For Ceftazidime Hydrolysis

Chemistry Faculty Publications

Gram-negative bacteria harboring KPC-2, a class A β-lactamase, are resistant to all β-lactam antibiotics and pose a major public health threat. Arg-164 is a conserved residue in all class A β-lactamases and is located in the solvent-exposed Ω-loop of KPC-2. To probe the role of this amino acid in KPC-2, we performed site-saturation mutagenesis. When compared with wild type, 11 of 19 variants at position Arg-164 in KPC-2 conferred increased resistance to the oxyimino-cephalosporin, ceftazidime (minimum inhibitory concentration; 32→128 mg/liter) when expressed in Escherichia coli. Using the R164S variant of KPC-2 as a representative β-lactamase for more detailed analysis, we …

Rnase L Controls Terminal Adipocyte Differentiation, Lipids Storage And Insulin Sensitivity Via Chop10 Mrna Regulation, O. Fabre, T. Salehzada, K. Lambert, Y. Boo Seok, Aimin Zhou, J. Mercier, C. Bisbal

Chemistry Faculty Publications

Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role of an endoribonuclease, endoribonuclease L (RNase L), using wild-type and RNase L-knockout mouse embryonic fibroblasts (RNase L^−/−-MEFs). Here, we identify C/EBP homologous protein 10 (CHOP10), a dominant negative member of the CCAAT/enhancer-binding protein family, as a specific RNase L target. We show that RNase L is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase …

Development And Validation Of A Rapid Lc-Ms/Ms Method Fortthe Determination Of Jcc76, A Novel Antitumor Agent For Breast Cancer, In Rat Plasma And Its Application To A Pharmacokinetics Study, Xiaohan Cai, Bo Zhong, Bin Su, Songlin Xu, Baochuan Guo

Chemistry Faculty Publications

JCC76 is a novel nimesulide analog that selectively inhibits the human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cell proliferation and tumor progression. To support further pharmacological and toxicological studies of JCC76, a novel and rapid method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the quantification of the compound in rat plasma. A C18 column was used for chromatographic separation, and the mobile phase was aqueous ammonium formate (pH 3.7; 5 mm)–methanol (1:9, v/v) with an isocratic elution. With a simple liquid–liquid extraction procedure using the mixture of methyl …

Identification Of Selective Tubulin Inhibitors As Potential Anti-Trypanosomal Agents, Rati Lama, Ranjodh Sandhu, Bo Zhong, Bibo Li, Bin Su

Chemistry Faculty Publications

The potency of a series of sulfonamide tubulin inhibitors against the growth of Trypanosoma brucei (T. brucei), as well as human cancer and primary fibroblast cells were evaluated with the aim of determining whether compounds that selectively inhibit parasite proliferation could be identified. Several compounds showed excellent selectivity against T. brucei growth, and have the potential to be used for the treatment of Human African trypanosomiasis. A T. brucei tubulin protein homology model was built based on the crystal structure of the bovine tubulin. The colchicine-binding domain, which is also the binding site of the tested sulfonamide tubulin inhibitors, showed …

The Effect Of The Charge-Separating Interface On Exciton Dynamics In Photocatalytic Colloidal Heteronanocrystals, Timothy O’Connor, Maxim S. Panov, Andrey Mereshchenko, Alexander N. Tarnovsky, Ryan Lorek, Dimuthu Perera, Geoffrey Diederich, Scott Lambright, Pavel Moroz, Mikhail Zamkov

Chemistry Faculty Publications

Ultrafast transient absorption spectroscopy was used to investigate the nature of photoinduced charge transfer processes taking place in ZnSe/CdS/Pt colloidal heteronanocrystals. These nanoparticles consist of a dot-in-a-rod semiconductor domain (ZnSe/CdS) coupled to a Pt tip. Together the three components are designed to dissociate an electron-hole pair by pinning the hole in the ZnSe domain while allowing the electron to transfer into the Pt tip. Separated charges can then induce a catalytic reaction, such as the light-driven hydrogen production. Present measurements demonstrate that the internal electron-hole separation is fast and results in the localization of both charges in nonadjacent parts of …

Experimental Determination Of Pka Values By Use Of Nmr Chemical Shifts, Revisited, Alan D. Gift

Chemistry Faculty Publications

This laboratory experiment, using proton NMR spectroscopy to determine the dissociation constant for heterocyclic bases, has been modified from a previously described experiment. A solution of a substituted pyridine is prepared using deuterium oxide (D2O) as the solvent. The pH of the solution is adjusted and proton NMR spectra are collected for a variety of pH values. The chemical shifts of the peaks in the NMR spectrum change depending on the degree of protonation of the pyridine ring. Analysis of the spectral data is used to calculate the dissociation constant of the substituted pyridine. This experiment is suitable for a …

Cr-Hollandite: Breaking Tradition With Todorokite-Type Manganese Oxides, Stanton Ching, Jonathan P. Franklin, Carley M. Spencer

Chemistry Faculty Publications

The synthesis of a tunneled hollandite-type manganese oxide with interstitial and framework Cr³⁺ is described. This unique material is prepared from a layered buserite precursor under conditions previously believed to only yield todorokite-type manganese oxides with larger tunnels. The influence of Cr³⁺ in promoting the hollandite structure has been investigated by selectively placing the cation either in interstitial or framework sites. The use of framework Cr³⁺ in combination with other interstitial cations generates related hollandite and todorokite derivatives. Catalytic oxidation reactions with benzyl alcohol and carbon monoxide have also been examined.

Origin Of Fluorescence In 11-Cis Locked Bovine Rhodopsin, Elena N. Laricheva, Samer Gozem, Silvia Rinaldi, Federico Melaccio, Alessio Valentini, Massimo Olivucci

Chemistry Faculty Publications

The excited state lifetime of bovine rhodopsin (Rh) increases from ca. 100 fs to 85 ps when the C11=C12 bond of its chromophore is locked by a cyclopentene moiety (Rh5). To explain such an increase, we employed ab initio multiconfigurational quantum chemistry to construct computer models of Rh and Rh5 and to investigate the shape of their excited state potential energy surfaces in a comparative way. Our results show that the observed Rh5 fluorescence (lambda(f)(max) = 620 nm) is due to a previously unreported locally excited intermediate whose lifetime is controlled by a small energy barrier. The analysis of the …

Understanding The Molecular Determinants Of Substrate And Inhibitor Specificities In The Carbapenemase Kpc-2: Exploring The Roles Of Arg220 And Glu276

Chemistry Faculty Publications

β-Lactamases are important antibiotic resistance determinants expressed by bacteria. By studying the mechanistic properties of β-lactamases, we can identify opportunities to circumvent resistance through the design of novel inhibitors. Comparative amino acid sequence analysis of class A β-lactamases reveals that many enzymes possess a localized positively charged residue (e.g., R220, R244, or R276) that is critical for interactions with β-lactams and β-lactamase inhibitors. To better understand the contribution of these residues to the catalytic process, we explored the roles of R220 and E276 in KPC-2, a class A β-lactamase that inactivates carbapenems and β-lactamase inhibitors. Our study reveals that substitutions …

Reactions Of Methyl Perfluoroalkyl Ethers With Isopropyl Alcohol: Experimental And Theoretical Studies, Howard Knachel, Vladimir Benin, Chadwick Barklay, Janine C. Birkbeck, Billy D. Faubion, William E. Moddeman

Chemistry Faculty Publications

The reaction of an isomeric mixture of the methyl perfluoroalkyl ether, C4F9OCH3 (Novec-7100), in the presence of isopropyl alcohol (IPA) and/or water has been studied by measuring the rate of product formation using an ion-selective electrode (ISE) for fluoride ion, Karl Fisher coulometric titrations for water, and 1H and 19F NMR spectroscopy for product identification and rate studies. The results showed the methyl perfluoroalkyl ether to be very stable with products forming at the rate of ∼1 ppm per year at a laboratory temperature of 20 °C. Measurements over the temperature range of 6° to 100 °C were made on …

En Route Towards Α-Benzotriazoyl Nitroso Derivatives, Jean-Christophe M. Monbaliu, Lucas K. Beagle, Judit K. Beagle, Matthias Zeller, Christian V. Stevens, Alan R. Katritzky

Chemistry Faculty Publications

A new class of geminally-substituted nitroso compounds, i.e., α-benzotriazoyl nitroso derivatives, is presented. These compounds display a rather different behavior than other related nitroso compounds bearing a geminal electron-withdrawing group. An unexpected and spontaneous oxidation to the nitro analog is observed in solution.

Development And Validation Of An Lc–Ms/Ms Method For Pharmacokinetic Study Of Methoxyamine In Phase I Clinical Trial, Shuming Yang, Panayiotis Savvides, Lili Liu, Stanton L. Gerson, Yan Xu

Chemistry Faculty Publications

Methoxyamine (MX) is the first DNA base-excision-repair (BER) inhibitor evaluated in humans. This work described the development and validation of an LC–MS/MS method for quantitative determination of MX in human plasma. In this method, MX and its stable isotope methoxyl-d3-amine (MX-d3 as internal standard) were directly derivatized in human plasma with 4-(N,N-diethylamino)benzaldehyde. The derivatized MX and IS were extracted by methyl-tert-butyl ether, and separated isocratically on a Xterra C18 column (2.1 mm × 100 mm) using an aqueous mobile phase containing 45% acetonitrile and 0.4% formic acid at a flow rate of 0.200 ml/min. Quantitation of MX was carried out …

Evolutionary History And Phylodynamics Of Influenza A And B Neuraminidase (Na) Genes Inferred From Large-Scale Sequence Analyses, Haizhen Zhong

Chemistry Faculty Publications

Background: Influenza neuraminidase (NA) is an important surface glycoprotein and plays a vital role in viral replication and drug development. The NA is found in influenza A and B viruses, with nine subtypes classified in influenza A. The complete knowledge of influenza NA evolutionary history and phylodynamics, although critical for the prevention and control of influenza epidemics and pandemics, remains lacking.

Methodology/Principal findings: Evolutionary and phylogenetic analyses of influenza NA sequences using Maximum Likelihood and Bayesian MCMC methods demonstrated that the divergence of influenza viruses into types A and B occurred earlier than the divergence of influenza A …

Mechanistic Study Of The Photochemical Hydroxide Ion Release From 9-Hydroxy-10-Methyl-9-Phenyl-9,10-Dihydroacridine, Dapeng Zhou, Renat Khatmullin, Janitha Walpita, Nicholas A. Miller, Hoi Ling Luk, Shubham Vyas, Christopher M. Hadad, Ksenija D. Glusac

Chemistry Faculty Publications

The excited-state behavior of 9-hydroxy-10-methyl-9-phenyl-9,10-dihydroacridine and its derivative, 9-methoxy-10-methyl-9-phenyl-9,10-dihydroacridine (AcrOR, R = H, Me), was studied via femtosecond and nanosecond UV-vis transient absorption spectroscopy. The solvent effects on C-O bond cleavage were clearly identified: a fast heterolytic cleavage (tau = 108 ps) was observed in protic solvents, while intersystem crossing was observed in aprotic solvents. Fast heterolysis generates 10methyl-9-phenylacridinium (Acr(+)) and -OH, which have a long recombination lifetime (no signal decay was observed within 100 mu s). AcrOH exhibits the characteristic behavior needed for its utilization as a chromophore in the pOH jump experiment.

6-Hydroximino-4-Aza-A-Homo-Cholest-3-One And Related Analogue As A Potent Inducer Of Apoptosis In Cancer Cells, Yanmin Huang, Jianguo Cui, Qiaoxia Zheng, Chun Zeng, Quan Chen, Aimin Zhou

Chemistry Faculty Publications

Here we report that 6-hydroximino-4-aza-A-homo-cholest-3-one and 6-hydroxyl-4-aza-A-homo-cholest-3-one, new steroidal lactams were synthesized recently, displayed antiproliferative activity against some cancer cells through inducing cancer cell apoptosis by activation of the intrinsic pathway. The apoptotic function of the compounds was demonstrated by release of cytochrome C, activation of caspase 3 and annexin V labeling. Furthermore, the compound was able to inhibit tumor growth in an athymic mouse model.