Induction of apoptosis by the inhibitors of poly(ADP-ribose)polymerase in HeLa cells

The poly( ADP ‐ribose) polymerases ( PARPs ) are located in the nuclei of cells and involved in DNA damage repair. PARP inhibitors have been used to target BRCA1 /2‐defective cells that experience increases in DNA single‐strand breaks ( SSBs ). In the presence of PAPR inhibitors, these SSBs are converted into irreparable and toxic double‐strand breaks ( DSBs ) during replication, eventually leading to cell death due to genome instability caused by the impaired homologous‐mediated repair system. We designed and synthesized several novel benzamide derivatives based on the previously reported PARP ‐1‐inhibitory activities of benzoxazole and benzamide moieties. Next, we used an in vitro assay to quantify their PARP ‐1 inhibitory activity and evaluate their potential as possible anti‐cancer therapeutics. Compound 28d contains a hydroxamate group and showed a significant inhibitory capacity ( IC 50 value of 3.2 μM ; 2.8‐ and 4.2‐fold decrease in SNU ‐251 and MDA‐MB ‐231 cells, respectively, compared with the DMSO ‐treated controls). Based on these results, we suggest that we have identified a novel hydroxybenzamide derivative of a benzamide moiety which is known as a key pharmacophore in existing PARP inhibitors.

Benzamide

Moiety

10.1002/bkcs.11207

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Inhibitors of poly(ADP‐ribose) polymerase suppress nuclear fragmentation and apoptotic‐body formation during apoptosis in HL‐60 cells

FEBS Letters (1997)

Daisuke Shiokawa Hideharu Maruta Sei-ichi Tanuma

The effects of 3-aminobenzamide (3ABm) and benzamide (BAm), known specific inhibitors of poly(ADP-ribose) polymerase (PARP), on actinomycin D (Act D)-induced apoptosis in HL-60 cells were examined. These inhibitors had no appreciable effect on apoptotic DNA fragmentation, chromatin condensation or PARP restriction cleavage, but clearly inhibited morphological changes, especially nuclear fragmentation and apoptotic-body formation, in a dose-dependent manner. These results suggest that the synthesis of ADP-ribose polymers is not essential for the progression of apoptotic DNA fragmentation and chromatin condensation, but is required in the processes leading to nuclear fragmentation and the subsequent apoptotic-body formation during apoptosis in HL-60 cells.

Fragmentation

Apoptotic DNA fragmentation

Apoptotic body

Benzamide

10.1016/s0014-5793(97)00887-9

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Citations (61)

Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11β-HSD1 inhibitors

Bioorganic & Medicinal Chemistry Letters (2009)

Yosup Rew Dustin L. McMinn Zhong Lin Wang Xiaodong He Randall W. Hungate

Benzamide

10.1016/j.bmcl.2009.01.058

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Synthesis of N‐(2,3‐dihydro‐1‐[¹⁴C]methyl‐2‐oxo‐5‐phenyl‐1H‐1,4‐benzodiazepin‐3‐yl)‐benzamide and N‐(2,3‐dihydro‐1‐[¹⁴C]methyl‐2‐oxo‐5‐phenyl‐1H‐1,4‐benzodiazepin‐3‐yl)‐N‐[¹⁴C]methyl‐benzamide as novel carbon‐14 labelled CCK antagonists

Journal of Labelled Compounds and Radiopharmaceuticals (2002)

Hojatollah Matloubi Ali Khalaj Reza Dowlatabadi Gholamhossein Shirvani

Abstract Two benzodiazepine CCK antagonists N ‐(2,3‐dihydro‐1‐[ 14 C]methyl‐2‐oxo‐5‐phenyl‐1H 1,4‐benzodiazepin‐3‐yl)‐benzamide 2 and N ‐(2,3‐dihydro‐1‐[ 14 C]methyl‐2‐oxo‐5‐phenyl‐1H‐1,4‐benzodiazepin‐3‐yl)‐[ 14 C]methyl‐benzamide 3 were synthesized in high yields through the reaction of N ‐(2,3‐dihydro‐2‐oxo‐5‐phenyl‐1H‐1,4‐benzodiazepin‐3‐yl)‐benzamide 1 with [ 14 C] methyl iodide in different situations. Copyright © 2002 John Wiley & Sons, Ltd.

Benzamide

Methyl iodide

10.1002/jlcr.555

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N-(2,4-Dichlorophenyl)benzamide

Acta Crystallographica Section E Structure Reports Online (2008)

B.T. Gowda M. Tokarčík Jozef Kožı́šek B.P. Sowmya H. Fueß

The conformations of the N—H and C=O bonds in the structure of the title compound, C13H9Cl2NO, are anti to each other, similar to that observed in N-phenylbenzamide, N-(2-chlorophenyl)benzamide, N-(4-chlorophenyl)benzamide, N-(2,3-dichlorophenyl)benzamide, N-(2,6-dichlorophenyl)benzamide and other benzanilides. The amide –NHCO– group forms a dihedral angle of 33.0 (2)° with the benzoyl ring, while the rings are almost coplanar, making a dihedral angle of 2.6 (2)°). The molecules are linked by N—H⋯O hydrogen bonds into infinite chains running along the b axis.

Benzamide

Dihedral angle

Amide

10.1107/s1600536808012385

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N-(4-Methylphenyl)benzamide

Acta Crystallographica Section E Structure Reports Online (2007)

B.T. Gowda M. Tokarčík Jozef Kožíšek B.P. Sowmya

The structure of the title compound, C(14)H(13)NO, resembles those of N-(2-chloro-phen-yl)benzamide, 2-chloro-N-phenyl-benzamide, N-(2,3-dichloro-phen-yl)benzamide, N-(3,4-dichloro-phen-yl)benzamide and 2-chloro-N-(2-chloro-phen-yl)benzamide with similar bond parameters. The benzene and methylphenyl rings have a dihedral angle of 63.41 (5)°, while the amide group makes a dihedral angle of 20.5 (1)° with the benzene ring. The mol-ecules are linked into chains in the b-axis direction by N-H⋯O hydrogen bonds.

Benzamide

Dihedral angle

Amide

10.1107/s1600536807061557

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NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes

Biochemical and Biophysical Research Communications (2003)

Weihai Ying Philippe Garnier Raymond A. Swanson

10.1016/s0006-291x(03)01483-9

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Citations (196)

Note Synthesis and antibacterial activity of benzamides and sulfonamide derived from 2- amino-5-bromo/nitropyridine against bacterial strains isolated from clinical patients

Diwakar Rai Ramendra K. Singh

A series of 5-(bromo/nitropyridin-2-yl)benzamide derivatives, viz. N-(5-bromopyridin-2-yl)benzamide 4a, 4-methyl-N-(5bromopyridin-2-yl)benzamide 4b, 4-chloro-N-(5-bromopyridin-2yl)benzamide 4c, 4-nitro-N-(5-bromopyridin-2-yl)benzamide 4d , N-(5-nitropyridin-2-yl)benzamide 7a, 4-methyl-N-(5-nitropyridin2-yl)benzamide 7b, 4-chloro-N-(5-nitropyridin-2-yl)benzamide 7c, 4-nitro-N-(5-nitropyridin-2-yl)benzamide 7c and a sulfonamide derivative, N-benzoyl-N-(5-bromopyridin-2-yl)trifluoromethane sulfonamide 5 have been synthesized as novel antibacterial agents. All compounds have shown promising activity (MIC 0.22–1.49 μM) against Gram-positive and Gram-negative bacterial strains using microdilution broth susceptibility test method. The sulfonamide 5 showed much better results than other compounds and its MIC values predicted it to be a lead compound as an antibacterial agent.

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Sulfonamide

Derivative (finance)

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Citations (8)