New tamoxifen analogs for breast cancer therapy: synthesis, aromatase inhibition and studies.

A new class of tamoxifen analogues, using McMurry reaction conditions, is described. The scheme involved the conversion of ketoprofen () into amide derivatives and , by coupling with -substituted propan-1,3-diamine derivatives in the presence DIC and HOB. Treatment of and with various ketones under McMurry reaction conditions afforded the tamoxifen analogues . All the analogues were screened for their aromatase inhibitory and antiproliferative activity against MCF-7 breast cancer cells. Compounds and showed a potent activity against MCF-7 cell lines breast cancer with IC values of 0.070, 0.042 and 0.077 µM of selectivity index (SI) 3.0, 2.5 and 2.6, respectively. Further, exhibited potent activity against estrogen receptor (14.7 ± 2.4 nM), while compound was the most active analogues against aromatase with IC50 of (0.070 nM). Furthermore, all new compounds were docked into human placental aromatase enzyme and estrogen receptor and showed very good correlations with experimental IC50. Therefore, we can consider these designed compounds as starting scaffold to design an efficient drug against estrogen receptor and aromatase.Communicated by Ramaswamy H. Sarma.