Pharmaceutical Chemistry Heterocyclic compounds as anticancer agents

Abstract

An approximately 2.1 million new breast cancer cases were diagnosed every year which makes it the most common cancer among women in the world. Around 70 percent of breast cancer patients are estrogen-dependent. Aromatase is the enzyme that distinguishes a man from women by converting androgens to estrogens. It is a rate limiting enzyme that characteristically binds C19 steroids with 4-ene-3-one system. Unfortunately it also triggers estrogen dependent breast cancers. The reduction of estrogen physiological concentration through aromatase inhibition is one of most important therapeutic strategies against postmenopausal breast cancer. Currently, the third-generation aromatase inhibitors (Anastrazole, Exemestane and Letrozole) are approved as front-line therapy for early and even advanced cases of breast cancer in postmenopausal women. However aromatase inhibitors chronic monotherapy or their combination with other targeted agents reported to develop resistance apart from consequential side effects. The quest for new class of aromatase inhibitors is essential to overcome the plausible resistance and unwanted side effects due to chronic therapy. Considering the magnitude for the necessity of newer generation aromatase inhibitors, the present research proposal aims at the design and synthesis of new series of heterocyclic rings like benzothiazole, benzimidazole 1,3,4-thiadiazole, imidazo[2,1-B][1,3,4]thiadiazole and thioureaderivatives as aromatase inhibitors in the treatment of cancer. The in-silico studies of ligand Based 3D QSAR Pharmacophore Modeling and Molecular docking studies were done to strengthen the rationale of the study. Finding of the in-silico studies have given some insights of selectivity of molecule and possible alternate binding interaction with important amino acids at the active site of aromatase. Based on the literature review different synthetic routes were adopted to synthesize aforementioned heterocyclic compounds and their derivatives. A new series of nitrogen-containing heterocyclic compou