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.
Keywords: Antiproliferative agents, Ishikawa Cell lines, Tetrahydroisoquinolines, Pharmacophore Models.
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