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91.
Reversible acetylation of histone and non-histone proteins plays an important role in the regulation of gene expression and cellular homeostasis. A balance between acetylation and deacetylation of these proteins are maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Among different HATs, p300/CBP is the most widely studied chromatin modifying enzymes. p300 is involved in several physiological processes like cell growth, regulation of gene expression, development, and tumor suppressor, and therefore its dysfunction causes different diseases. The autoacetylation of p300 is one of the key regulators of its catalytic activity. Mechanistically, autoacetylation induced structural changes in the p300 HAT domain acts as a master switch. In this report, we have shown that the natural HAT inhibitor garcinol could potently inhibit the autoacetylation activity. Furthermore, for the first time, we demonstrate that indeed autoacetylation induces structural changes in p300 HAT domain, as probed by surface-enhanced Raman scattering. Presumably, SERS will be a very useful tool to find out the structural changes in the other self-modifying enzymes like kinases and methyltransferases. 相似文献
92.
Mantelingu K Kishore AH Balasubramanyam K Kumar GV Altaf M Swamy SN Selvi R Das C Narayana C Rangappa KS Kundu TK 《The journal of physical chemistry. B》2007,111(17):4527-4534
Reversible acetylation of nucleosomal histones and nonhistone proteins play pivotal roles in the regulation of all the DNA templated phenomenon. Dysfunction of the enzymes involved in the acetylation/deacetylation leads to several diseases. Therefore, these enzymes are the targets for new generation therapeutics. Here, we report the synthesis of trifluoromethyl phenyl benzamides and their effect on histone acetyltransferase (HAT) activity of p300. One of these benzamides, CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), was discovered as a potent activator of the p300 HAT activity. We have found that pentadecyl hydrocarbon chain of CTPB is required to activate the HAT only under certain context. Furthermore, our results show that the relative position of -CF3 and -Cl in CTB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide) is also very critical for the activation. Surface-enhanced Raman spectroscopy (SERS) of p300 and the HAT activator complexes evidently suggest that the activation of HAT activity is achieved by the alteration of p300 structure. Therefore, apart from elucidating the chemical basis for small molecule mediated activation of p300, this report also describes, for the first time, Raman spectroscopic analysis of the complexes of histone-modifying enzymes and their modulators, which may be highly useful for therapeutic applications. 相似文献
93.
Goravanahalli M. Raghavendra Chottanahalli S. Pavan Kumar Gejjalagere P. Suresha Kanchugarakoppal S. Rangappa Kempegowda Mantelingu 《中国化学快报》2015,26(8):963-968
An efficient methodology for the synthesis of 2,3-disubstituted 3H-quinazolin-4-ones is described via one-pot three component reaction from anthranilic acid using T3P as catalyst. Mild reaction conditions, short reaction time, broad functional group tolerance, easy isolation of products and good yields are main advantages of this protocol. 相似文献
94.
95.
Mamatha Serasanambati Shanmuga Reddy Chilakapati Pavan Kumar Manikonda Jagadeeswara Reddy Kanala 《Natural product research》2015,29(5):484-490
This study was designed to investigate the combination effects of brucine and gemcitabine, each with anticancer properties, in MCF-7 human breast cancer cells in culture. With regard to cell viability, effects of both the drugs and their combinations were inversely proportional to dose and time. For various proportional drug combinations studied, combination effects were analysed using CompuSyn software. The analyses revealed synergistic and/or additive effects regarding cell viability, anchorage-independent growth and cell migration. Combination analyses exhibited diversified impacts of the type of combination treatment, namely pretreatment with either drug followed by exposure to the other, or treatment with both drugs at the same time. Compared with untreated cells, combination treatment of asynchronised MCF-7 cells resulted in 17.2 × decrease in G2 phase, increasing G1 (2.1 × ) and S (1.5 × ) phase cells in cell cycle analysis. Brucine, either individually or in combination, but not gemcitabine, inhibited NF-kB subunit (p65) expression in MCF-7 cells. 相似文献
96.
Parkinson’s disease (PD) is a degenerative disorder of the CNS, characterized by cerebral depletion of dopamine (DA), hence one of the approaches to delay the depletion of DA is to inhibit its oxidative deamination. Monoamine oxidases (MAO) carry out the oxidative deamination of monoamines like DA. These are intracellular enzymes, located on the outer mitochondrial membrane. MAO-A and MAO-B are the two subtypes of which MAO-B is the most predominant enzyme and is commonly found in the brain. Inhibition of the MAO-B enzyme boosts the effect of both endogenous and exogenous DA. In this study, we have carried out crystal structure analysis and structure-based design of MAO-B inhibitors. We also performed molecular dynamics, flexible docking, induced-fit docking and ADME prediction of the newly designed compounds. 相似文献
97.
A new fluorescent probe based on a bis-benzimidazole diamide N 2,N 2′-bis[(1-ethyl-benzimidazol-2-yl)methyl]biphenyl-2,2′-dicarboxamide ligand L 1 with a biphenyl spacer group and a Copper(II) trinuclear metallacycle has been synthesized and characterized by X-ray single crystallography, elemental and spectral (FT-IR, 1H & 13C NMR, UV-Visible) analysis. The fluorescence spectra of L 1 in MeOH show an emission band centered at 300 nm. This band arises due to benzimidazolyl moiety in the ligating system. The diamide L 1 in the presence of Cu2+ show the simultaneous ‘quenching’ of (300 nm) and ‘enhancement’ of (375 nm) emission band. Similar fluorescence behavior was found in water–methanol mixture (9:1). The new emission band at 375 nm is attributed to intra ligand π–π* transition of the biphenyl moiety. L 1 exhibited high selectivity and sensitivity towards Cu2+ in both the medium over other common metal ions like Ni2+, Co2+, Mn2+, Mg2+, Zn2+, Pb2+ and Hg2+. The binding constant with Cu2+ was calculated by the Benesi-Hildebrand equation. Selective “off-on-off” behavior of L 1 in methanol has also been studied. The fluorescent intensity of 375 nm bands in L 1 enhances (turns-on) upon addition of Cu2+ and quenches (turn-off) upon addition of Na2-EDTA. 相似文献
98.
Chiguru Srinivas Chebolu Naga Sesha Sai Pavan Kumar Bhimapaka China Raju Vaidya Jayathirtha Rao 《Helvetica chimica acta》2011,94(4):669-674
An efficient stereoselective total synthesis of (+)‐(4S,5S)‐muricatacin was accomplished in good yields from inexpensive, commercially available chemicals ((+)‐diethyl tartrate (DET) and undecan‐1‐ol) by utilizing Mitsunobu and Julia? Kocienski reactions, Wittig homologation, Swern oxidation, and lactonization. 相似文献
99.
Synthesis, spectral and catalytic activity of some manganese(II) bis-benzimidazole diamide complexes
Mohapatra SC Hundal MS Mathur P 《Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy》2011,79(5):1634-1641
Four Mn(II) complexes bound to a neutral bis-benzimidazole diamide ligand N,N'-bis(2-methyl benzimidazolyl 2,2'-oxy-diethanamide) (GBOA) have been synthesized and characterized. Anionic ligand associated with the complexes varies as Cl- CH3COO-, SCN- and ClO4-. X-ray structure of one of the complexes [Mn(GBOA)2(H2O)2]Cl(2)·4H2O was solved and shows that the Mn(II) ion is hexacoordinate. Two equatorial positions are occupied by benzimidazole imine nitrogen atoms while the other two sites are occupied by amide carbonyl oxygens. The imine nitrogen and carbonyl oxygens are bound to Mn(II) by different arms of the two ligands while axial sites are occupied by two water molecules. Two Cl- anions are outside the coordination sphere and form an extensive 3D H-bonded network. Axially distorted octahedral geometry is confirmed for all the four complexes by low temperature EPR spectroscopy. Distortion parameter D was found to be similar for [Mn(GBOA)2(H2O)2]Cl(2)·4H2O and [Mn(GBOA)2(H2O)2]·(CH3COO)2·H2O. Cyclic voltammograms have been obtained for all the four complexes and E(1/2) values are dependent on the anionic ligand being in the coordination sphere or outside. [Mn(GBOA)2(H2O)2]Cl(2)·4H2O and [Mn(GBOA)2(H2O)2]·(CH3COO)2·H2O carry out the selective oxidation of N-benzyldimethylamine, and 1-methyl-pyrollidine to their respective carbonyl products with catalytic efficiency of 35-50%. 相似文献
100.
Mohapatra SC Mathur P 《Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy》2011,78(2):612-616
Monomeric Cu(II) and Cu(I) complexes bound to a tetradentate bis-benzimidazole diamide ligand N,N'-bis(N-octyl benzimidazolyl-2yl)(methyl)pentane diamide (O-GBGA) have been isolated and characterized. X-Band EPR spectra of the copper(II) complexes in CH2Cl2 were recorded in a frozen solution as solvent at liquid nitrogen temperature. Solution spectra typically indicate a d(x2-y2) ground state (g||>g⊥>2.0023) and show less than four nuclear hyperfine lines with broadening of g⊥ line in some cases, thus indicating distorted tetragonal geometry. One of the copper(II) complexes shows a five line N-SHF structure (16±1G) implying the binding of imine nitrogen of the benzimidazole to copper ion. α2 ranges from 0.57-0.97 indicating considerable amount of covalent character in Cu-L bond. Anodic shifts in E1/2 values indicate the retention of anion in the coordination sphere of Cu(II), E1/2 values becoming anodic in the order C6H5COO-相似文献