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Letters in Drug Design & Discovery
ISSN (Print): 1570-1808
ISSN (Online): 1875-628X
VOLUME: 11
ISSUE: 4
DOI: 10.2174/1570180811666131203002502      Price:  $58









In-Vitro Antiproliferative Activity of New Tetrahydroisoquinolines (THIQs) on Ishikawa Cells and their 3D Pharmacophore Models

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Author(s): Suresh Kumar V. K. Eyunni, Madhavi Gangapuram and Kinfe K. Redda
Pages 428-436 (9)
Abstract:
The antiproliferative activities of new substituted tetrahydroisoquinolines (THIQs) are described. Their cytotoxicities against Ishikawa human endometrial cell line were determined after 72 h drug expose employing Celtiter-Glo assay at concentrations ranging from 0.01 to 100,000 nM. The antiproliferative activities of the compounds understudy were compared to 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 1, 2, 3 and 22 whose IC50 values are 1.41, 0.91, 0.74 and 0.36 µM respectively. This study helped us to evaluate the risk of developing endometrial cancer in the design of nonsteroid estrogen receptor modulators with no agonistic effects on uterus. In-silico pharmacophore hypotheses were generated using GALAHAD and PHASE and the best models with a probable bioactive conformation(s) for these compounds were proposed. These conformations and the alignments of the molecular structures give us an insight in designing compounds with better biological activity.
Graphical Abstract:
Keywords:
Antiproliferative agents, Ishikawa Cell lines, Tetrahydroisoquinolines, Pharmacophore Models.
Affiliation:
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA.