Design, synthesis and anticancer activity of dihydropyrimidinone–semicarbazone hybrids as potential human DNA ligase 1 inhibitors

A total of 19 anthracycline derivatives were tested for their ability to interfere in vitro with the action of the human replicative DNA ligase. Only those with the sugar devoid of unmodified amino groups or with large configurational modifications were found to be inactive. Maximal inhibition of DNA-joining activity was found to require a 4′-deoxy-3′-amino sugar. Self-adenylation of DNA ligase was largely insensitive to these drugs. An important general finding is that slight modifications of the anthracycline structure have pronounced effects on DNA-ligase-inhibitory activity and might be related to the specificity of anthracycline anti-tumour activity.

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De Novo Design, Synthesis, and In Vitro Evaluation of a New Class of Nonpeptidic Inhibitors of the Malarial Enzyme Plasmepsin II

ChemBioChem ◽

10.1002/1439-7633(20021104)3:11<1137::aid-cbic1137>3.0.co;2-a ◽

2002 ◽

Vol 3 (11) ◽

pp. 1137-1141 ◽

Cited By ~ 27

Author(s):

David A. Carcache ◽

Simone R. Hörtner ◽

Andreas Bertogg ◽

Christoph Binkert ◽

Daniel Bur ◽

...

Keyword(s):

De Novo ◽

De Novo Design ◽

Design Synthesis ◽

In Vitro Evaluation ◽

New Class ◽

Plasmepsin Ii

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In Vitro and In Vivo Interactions of DNA Ligase IV with a Subunit of the Condensin Complex

Molecular Biology of the Cell ◽

10.1091/mbc.e01-11-0117 ◽

2003 ◽

Vol 14 (2) ◽

pp. 685-697 ◽

Cited By ~ 18

Author(s):

Marcin R. Przewloka ◽

Paige E. Pardington ◽

Steven M. Yannone ◽

David J. Chen ◽

Robert B. Cary

Keyword(s):

Molecular Mechanisms ◽

Critical Role ◽

Dna Ligase ◽

Mitotic Chromosomes ◽

Dna Ligase Iv ◽

Cell Extracts ◽

Condensin Complex ◽

Human Dna ◽

Ligase Iv

Several findings have revealed a likely role for DNA ligase IV, and interacting protein XRCC4, in the final steps of mammalian DNA double-strand break repair. Recent evidence suggests that the human DNA ligase IV protein plays a critical role in the maintenance of genomic stability. To identify protein–protein interactions that may shed further light on the molecular mechanisms of DSB repair and the biological roles of human DNA ligase IV, we have used the yeast two-hybrid system in conjunction with traditional biochemical methods. These efforts have resulted in the identification of a physical association between the DNA ligase IV polypeptide and the human condensin subunit known as hCAP-E. The hCAP-E polypeptide, a member of the Structural Maintenance of Chromosomes (SMC) super-family of proteins, coimmunoprecipitates from cell extracts with DNA ligase IV. Immunofluorescence studies reveal colocalization of DNA ligase IV and hCAP-E in the interphase nucleus, whereas mitotic cells display colocalization of both polypeptides on mitotic chromosomes. Strikingly, the XRCC4 protein is excluded from the area of mitotic chromosomes, suggesting the formation of specialized DNA ligase IV complexes subject to cell cycle regulation. We discuss our findings in light of known and hypothesized roles for ligase IV and the condensin complex.

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Synthesis and preliminary evaluation of the anti-cancer activity on A549 lung cancer cells of a series of unsaturated disulfides

MedChemComm ◽

10.1039/c8md00503f ◽

2019 ◽

Vol 10 (1) ◽

pp. 116-119 ◽

Cited By ~ 2

Author(s):

Fabrizio Olivito ◽

Nicola Amodio ◽

Maria Luisa Di Gioia ◽

Monica Nardi ◽

Manuela Oliverio ◽

...

Keyword(s):

Lung Cancer ◽

Anticancer Activity ◽

Cancer Cells ◽

Lung Cancer Cells ◽

Preliminary Evaluation ◽

Natural Analogue ◽

Anti Cancer ◽

A549 Lung ◽

Cancer Activity

In this work we synthesized and tested a series of unsaturated disulfides. Two compounds showed a promising anticancer activity in vitro on A549 lung cancer cells compared to the natural analogue.

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Design, Synthesis, SAR Study, Antimicrobial and Anticancer Evaluation of Novel 2-Mercaptobenzimidazole Azomethine Derivatives

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557518666180903151849 ◽

2020 ◽

Vol 20 (15) ◽

pp. 1559-1571 ◽

Cited By ~ 6

Author(s):

Sumit Tahlan ◽

Balasubramanian Narasimhan ◽

Siong Meng Lim ◽

Kalavathy Ramasamy ◽

Vasudevan Mani ◽

...

Keyword(s):

Anticancer Activity ◽

Anticancer Agents ◽

Benzimidazole Derivatives ◽

Dilution Method ◽

Anticancer Activities ◽

Design Synthesis ◽

Standard Drug ◽

Wide Range ◽

Sar Study

Background: Various analogues of benzimidazole are found to be biologically and therapeutically potent against several ailments. Benzimidazole when attached with heterocyclic rings has shown wide range of potential activities. So, from the above provided facts, we altered benzimidazole derivatives so that more potent antagonists could be developed. In the search for a new category of antimicrobial and anticancer agents, novel azomethine of 2-mercaptobenzimidazole derived from 3-(2- (1H-benzo[d]imidazol-2-ylthio)acetamido)benzohydrazide were synthesized. Results and Discussion: The synthesized analogues were characterized by FT-IR, 1H/13C-NMR and MS studies as well C, H, N analysis. All synthesized compounds were evaluated for in vitro antibacterial activity against Gram-positive (B. subtilis), Gram-negative (E. coli, P. aeruginosa, K. pneumoniae and S. typhi) strains and in vitro antifungal activity against C. albicans and A. niger strains by serial dilution method, the minimum inhibitory concentration (MIC) described in μM/ml. The in vitro anticancer activity of synthesized compounds was determined against human colorectal carcinoma cell line (HCT- 116) using 5-fluorouracil as standard drug. Conclusion: In general, most of the synthesized derivatives exhibited significant antimicrobial and anticancer activities. Compounds 8, 10, 15, 16, 17, 20 and 22 showed significant antimicrobial activity towards tested bacterial and fungal strains and compound 26 exhibited significant anticancer activity.

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