Abstract
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.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis and Biological Evaluation of Diaryl Ether Linked DC-81 Conjugates as Potential Antitumor Agents
Volume: 13 Issue: 10
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 and Manika pal Bhadra
Affiliation:
Keywords: Anticancer activity, apoptosis, caspase, diaryl ether, mitochondrial membrane potential, poly-(ADP-ribose) polymerase, pyrrolobenzodiazepines.
Abstract: 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.
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Kamal Ahmed, Viswanath A., Ramaiah Janaki M., Murty N.S.R.C. J., Sultana Farheen, Bharathi Vijaya E., Ramakrishna G., Sarma Pranjal, Lavanya A., Pushpavalli N.C.V.L. S. and Bhadra pal Manika, Synthesis and Biological Evaluation of Diaryl Ether Linked DC-81 Conjugates as Potential Antitumor Agents, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/1871520613666131125122408
DOI https://dx.doi.org/10.2174/1871520613666131125122408 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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