Abstract

DESIGN, SYNTHESIS AND ESTROGEN RECEPTOR MODULATION ACTIVITY OF MODIFIED RALOXIFENE ANALOGUES

*Maninderjeet Kaur, Jasreen Kaur, Amit Kapoor, Dr. Jatinder Bariwal, Mandeep Kaur and Poonam Verma

ABSTRACT

Cancer refers to a group of disease that result from the abnormal cells growing in the body. Breast cancer is the most commonly cancer in women. Selective Estrogen Receptor Modulators (SERMs) are a class of compounds that can modulate the estrogen receptor (ER) as agonists or antagonists depending upon the tissue involved. Raloxifene is one of the widely used SERM but suffers from some undesirable side effects. Thus, we have selected Raloxifene as a lead compound for new modifications, to improve the selectivity and potency of the drug. Thiophene o-aminoesters (IIIa-b) are easily synthesized by the condensation of α-methylene carbonyl compounds with α-cyano ester and sulfur in presence of diethylamine (secondary aliphatic amine) at room temperature (Gewald Reaction). Intermediate 2-chloroacetamide V(a-b) were accessed synthesized as per Scheme-20 by reacting thiophene-o-aminoesters (IIIa-b) and chloroacetylchloride in presence of pyridine in benzene as solvent.The targeted compounds VI(a-h) and VII(a-g) were synthesized from compound V(a-b) by reacting with various aliphatic or aromatic amines in the presence of aprotic solvent acetonitrile. The newly synthesized compounds VI(a-h) and VII(a-g) have been characterized by various analytical techniques such as FTIR, 1HNMR and Mass spectroscopy. All the newly synthesized compounds VI(a-h)&VII(a-g) were evaluated against the breast cancer cell lines, i.e., MCF-7 and T-47-D in the animal tissue culture laboratory at ISFCP, Moga using MTT assay. Some of the compounds from this series show potent cytotoxic effects on MCF-7 and T-47-D cell lines.

Keywords: Cancer, Estrogen receptor, Raloxifene analogues, Thiophene analogues, Gewald Reaction, FTIR, 1H NMR, MTT assay.