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

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.

Cite this article as:

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