nsc-706744 and oxynitidine

nsc-706744 has been researched along with oxynitidine* in 1 studies

Other Studies

1 other study(ies) available for nsc-706744 and oxynitidine

Article	Year
Discovery, Synthesis, and Evaluation of Oxynitidine Derivatives as Dual Inhibitors of DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1), and Potential Antitumor Agents. Journal of medicinal chemistry, 2018, 11-21, Volume: 61, Issue:22 Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a recently discovered enzyme repairing DNA lesions resulting from stalled topoisomerase IB (TOP1)-DNA covalent complex. Inhibiting TDP1 in conjunction with TOP1 inhibitors can boost the action of the latter. Herein, we report the discovery of the natural product oxynitidine scaffold as a novel chemotype for the development of TOP1 and TDP1 inhibitors. Three kinds of analogues, benzophenanthridinone, dihydrobenzophenanthridine, and benzophenanthridine derivatives, were synthesized and evaluated for both TOP1 and TDP1 inhibition and cytotoxicity. Analogue 19a showed high TOP1 inhibition (+++) and induced the formation of cellular TOP1cc and DNA damage, resulting in cancer cells apoptosis at nanomolar concentration range. In vivo studies indicated that 19a exhibits antitumor efficiency in HCT116 xenograft model. 41a exhibited additional TDP1 inhibition with IC Topics: Antineoplastic Agents; Cell Line, Tumor; Chemistry Techniques, Synthetic; DNA Cleavage; DNA Topoisomerases, Type I; Drug Design; Humans; Models, Molecular; Phenanthridines; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Protein Conformation; Structure-Activity Relationship; Topoisomerase I Inhibitors	2018

Article

Year

Discovery, Synthesis, and Evaluation of Oxynitidine Derivatives as Dual Inhibitors of DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1), and Potential Antitumor Agents.

Journal of medicinal chemistry, 2018, 11-21, Volume: 61, Issue:22

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a recently discovered enzyme repairing DNA lesions resulting from stalled topoisomerase IB (TOP1)-DNA covalent complex. Inhibiting TDP1 in conjunction with TOP1 inhibitors can boost the action of the latter. Herein, we report the discovery of the natural product oxynitidine scaffold as a novel chemotype for the development of TOP1 and TDP1 inhibitors. Three kinds of analogues, benzophenanthridinone, dihydrobenzophenanthridine, and benzophenanthridine derivatives, were synthesized and evaluated for both TOP1 and TDP1 inhibition and cytotoxicity. Analogue 19a showed high TOP1 inhibition (+++) and induced the formation of cellular TOP1cc and DNA damage, resulting in cancer cells apoptosis at nanomolar concentration range. In vivo studies indicated that 19a exhibits antitumor efficiency in HCT116 xenograft model. 41a exhibited additional TDP1 inhibition with IC

Topics: Antineoplastic Agents; Cell Line, Tumor; Chemistry Techniques, Synthetic; DNA Cleavage; DNA Topoisomerases, Type I; Drug Design; Humans; Models, Molecular; Phenanthridines; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Protein Conformation; Structure-Activity Relationship; Topoisomerase I Inhibitors

2018