Synthesis and Biological Evaluation of Diaryl Ether Linked DC-81 Conjugates as Potential Antitumor Agents

Author(s): Ahmed Kamal, A. Viswanath, M. Janaki Ramaiah, J. N.S.R.C. Murty, Farheen Sultana, E. Vijaya Bharathi, G. Ramakrishna, Pranjal Sarma, A. Lavanya, S. N.C.V.L. Pushpavalli, Manika pal Bhadra

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 13 , Issue 10 , 2013

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A series of new diaryl ether linked pyrrolobenzodiazepine (PBD) conjugates (4a-i, 5a-i and 6a-f) was synthesized and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. These conjugates exhibited significant anticancer activity with GI50 values in the range of 0.1-3.88 μM. Some of the potent conjugates (4b, 4h, 5h, 6b, 6c and 6e) were further investigated on cell cycle distribution. FACS analysis showed the accumulation of cells in G0 phase indicating the apoptosis inducing nature of these conjugates. Moreover, compound 6b caused a decrease in the mitochondrial membrane potential, which indicates the apoptotic nature of the compound through mitochondrial mediated pathway. Further conjugates 4b, 4h and 6b induce the activation of caspase and PARP proteins, followed by apoptotic cell death in MCF7 cell line.

Keywords: Anticancer activity, apoptosis, caspase, diaryl ether, mitochondrial membrane potential, poly-(ADP-ribose) polymerase, pyrrolobenzodiazepines.

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Article Details

Year: 2013
Page: [1590 - 1600]
Pages: 11
DOI: 10.2174/1871520613666131125122408
Price: $65

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