Synthesis and antitumor activity of novel enediyne-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids

Bioorganic & Medicinal Chemistry
Wan-Ping HuJeh-Jeng Wang

Abstract

A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with enediyne is described. These compounds were prepared by linking C-8 of DC-81 (1) with an enediyne (10-16) through carbon chain linkers to afford PBD hybrid agents 17-23 in good yields. Most of the hybrids on human cancer cell lines exhibited higher cytotoxicity, and an increase in the sub-G1 population than 1. In a previous article, we have demonstrated that DC-81-indole conjugate agents (3-6) are potent inducers of cell apoptosis in melanoma. In the present article, we investigated whether DC-81-enediyne agents possess more cytotoxicity than 6 on human 293T cells. Our data revealed that treatment of 293T cells with DC-81-enediyne resulted in a significant increase of annexin V binding, caspase-3 degradation, and p53 arrest to identify apoptotic cells than 6. These results suggest that the DC-81-enediyne agents are more efficient in inducing apoptosis than DC-81-indole in 293T cells.

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Citations

Dec 21, 2010·Chemical Reviews·Dyeison Antonow, David E Thurston
Jun 15, 2010·Medicinal Research Reviews·Barbara Gerratana
Feb 8, 2011·Organic & Biomolecular Chemistry·Susana HernándezEsther Domínguez
Mar 17, 2012·Chemistry & Biodiversity·Mukesh C Joshi, Diwan S Rawat
Apr 14, 2021·Medicinal Research Reviews·Guna SakaineGints Smits

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