Structure-based Drug Design and Synthesis of PARP Inhibitors

Manikanta Murahari

ISBN 10: 6200437785 / ISBN 13: 9786200437785

Editore: LAP LAMBERT Academic Publishing Okt 2019, 2019

Riguardo questo articolo

Neuware -Poly(ADP-ribose)polymerase (PARP) is a chromatin bound nuclear enzyme which gets activated by DNA breaks, uses NAD as substrate and catalyses the poly-ADP ribosylation of a variety of proteins. The enzyme PARP is considered as a suitable target for anti-cancer activity as it is involved in a variety of physiological functions like cellular proliferation, differentiation, apoptosis and DNA replication. Based on the literature, pharmacophoric templates and bio-isosteric replacement approach, quinazolinone and phthalazinone derivatives were selected to design molecules to calculate binding affinity and visualize binding conformations and interactions at the active pocket of target PARP-1 protein. For preliminary evaluation, in silico potential compounds were selected to synthesize, purified by column chromatography, characterized by HNMR and Mass Spectral studies and carried out for in vitro cytotoxicity. Molecular docking and preliminary experimental data helped to investigate Structure Activity Relationship for design of safe and potential PARP-1 inhibitors for cancer therapy.Books on Demand GmbH, Überseering 33, 22297 Hamburg 108 pp. Englisch.

Codice articolo 9786200437785

Dati bibliografici

• Titolo: Structure-based Drug Design and Synthesis of PARP Inhibitors
• Editore: LAP LAMBERT Academic Publishing Okt 2019
• Data di pubblicazione: 2019
• Lingua: Inglese
• ISBN 10: 6200437785
• ISBN 13: 9786200437785
• Rilegatura: Taschenbuch
• Condizione: Neu
• Dimensioni: 220 L x 150 A x 7 P (millimetri) 220 millimetri di larghezza per 150 millimetri di altezza per 7 millimetri di profondità
• Peso: 179 grammi

Descrizione articolo

Riassunto

Poly(ADP-ribose)polymerase (PARP) is a chromatin bound nuclear enzyme which gets activated by DNA breaks, uses NAD as substrate and catalyses the poly-ADP ribosylation of a variety of proteins. The enzyme PARP is considered as a suitable target for anti-cancer activity as it is involved in a variety of physiological functions like cellular proliferation, differentiation, apoptosis and DNA replication. Based on the literature, pharmacophoric templates and bio-isosteric replacement approach, quinazolinone and phthalazinone derivatives were selected to design molecules to calculate binding affinity and visualize binding conformations and interactions at the active pocket of target PARP-1 protein. For preliminary evaluation, in silico potential compounds were selected to synthesize, purified by column chromatography, characterized by HNMR and Mass Spectral studies and carried out for in vitro cytotoxicity. Molecular docking and preliminary experimental data helped to investigate Structure Activity Relationship for design of safe and potential PARP-1 inhibitors for cancer therapy.