Synthesis, anticancer activity and mitochondrial mediated apoptosis inducing ability of 2,5-diaryloxadiazole-pyrrolobenzodiazepine conjugates

Bioorganic & Medicinal Chemistry
Ahmed KamalSurekha Zingde

Abstract

A series of 2,5-diaryloxadiazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates have been prepared and evaluated for their anticancer activity. These conjugates have shown promising activity with GI50 values ranging from <0.1 to 0.29 microM. It is observed that some of these conjugates particularly 4a, 4d, 4i and 4l exhibit significant anticancer activity. Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates.

References

Mar 9, 1995·Nature·D O Morgan
Aug 1, 1997·Trends in Biochemical Sciences·D W Nicholson, N A Thornberry
Dec 9, 1997·Cell·G S Salvesen, V M Dixit
Sep 12, 1998·Science·J M Adams, S Cory
Apr 13, 2004·Oncogene·Klaus-Michael Debatin, Peter H Krammer
Dec 1, 2005·Molecular Cancer Research : MCR·Cécile-Marie Aliouat-DenisJorge E Vialard

Related Concepts

Antineoplastic Agents
Benzodiazepines
Cell Cycle
Mitochondria
Malignant Neoplasms
Oxadiazoles
Protein p53
Mice, Inbred NOD
Apoptosis, Intrinsic Pathway
Caspase

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