Synthesis and Pharmacological Evolution of Tetrahydroisoquinolines as Anti Breast Cancer Agents
Madhavi Gangapuram, Suresh Eyunni and Kinfe K Redda*
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA
- *Corresponding Author:
- Kinfe K. Redda, Ph.D
Professor & V.P. for Research
College of Pharmacy & Pharmaceutical Sciences
Florida A & M University, 410 Foote-Hilyer Administration Center
Division of Research, Tallahassee, FL 32307, USA
E-mail: [email protected]
Received Date: March 11, 2014; Accepted Date: April 18, 2014; Published Date: April 25, 2014
Citation: Gangapuram M, Eyunni S, Redda KK (2014) Synthesis and Pharmacological Evolution of Tetrahydroisoquinolines as Anti Breast Cancer Agents. J Cancer Sci Ther 6:161-169. doi: 10.4172/1948-5956.1000266
Copyright: © 2014 Gangapuram M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Breast cancer is leading cause of mortality among women, resulting in more than half a million deaths worldwide each year. Unfortunately, the recovery rate of advanced breast cancer by current available drug treatment is till unacceptably low. Chemotherapy is the main stay of cancer treatment and most of the drugs cause general toxicity to any non-proliferating cells, which can severely limit the therapeutic values of these drugs. Tetrahydroisoqinoline derivatives (THIQs) were identified as subtype selective estrogen receptor antagonists/agonists hence, potential therapeutic agents for breast cancer. Substituted THIQs were synthesized and well characterized. Antiproliferative activity against human ER (+) MCF-7 (Breast), ER(-) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines were studied after 72 hours drug exposure employing CellTiter-Glo assay at concentrations ranging from 0.01- 100,000 nM. The activities of these compounds were compared with Tamoxifen (TAM). In-vitro results indicated that most of the compounds showed better activity than TAM. The most active compounds obtained in this study were 6a, 6b, 6d and 6j (IC50=0.63, 0.23; 0.93, 0.21; 043, 0.01; 0.7, 0.02 μg/ml) against MCF-7 and Ishikawa cell lines, in comparison to Tamoxifen activity (IC50=5.14, 4.55 μg/ml). The newly synthesized molecules were docked in the active sites of the ER-α (PDB: 3ERT) and ER-β (PDB: 3ERT) crystal structures and probable binding modes of this class of molecules were determined.