In Silico Design, Synthesis and Bioactivity of N-(2, 4-Dinitrophenyl)-3-oxo- 3-phenyl-N-(aryl) Phenyl Propanamide Derivatives as Breast Cancer Inhibitors.

BACKGROUND: Breast cancer is a systemic disease which has challenged physicians worldwide as it is the most predominant cancer in women often leading to fatality. One of the types of treatment is chemotherapy which includes targeted oral or intravenous cancer-killing drugs. Treatment options are often limited to surgery and/or chemotherapy. OBJECTIVE: The discovery and design of new small molecule estrogen inhibitors is necessitated in order to circumvent the problem of drug-induced resistance in chemotherapy resulting in disease relapse. Chemoinformatics facilitates the design, selection and synthesis of new drug candidates for breast cancer by providing efficient in silico techniques for prediction of favourable ADMET properties, and structural descriptors to profile druggability of a compound. METHOD: Several molecules selected from docking studies were synthesized and evaluated for their biological activities on the MCF-7 (human breast cancer) cell line. RESULTS: These estrogen inhibitors displayed good inhibitory activity with high selectivity and hence can be further progressed as drug candidates effective against breast cancer. CONCLUSION: It is for the first time that N-(2, 4-dinitrophenyl)-3-oxo-3-phenyl-N-(aryl) phenylpropanamide derivatives were reported to be biological active as potential breast cancer inhibitors.

Domino Reactions in Drug Design and Discovery.

With reference to challenges in developing varied and exceedingly complex scaffolds expeditiously through atom economy, domino reactions have assumed a significant role in several transformative endeavors towards established pharmaceuticals and new chemical entities across diverse therapeutic classes such as HIV integrase inhibitors, DPP4 [dipeptidyl peptidase IV] inhibitors, GSK- 3 (Glycogen Synthase Kinase 3) inhibitors, neoplastic drugs and microtubule antagonists. The very large chemical space of Domino Reactions can be leveraged for the design strategy of drugs and drug- like candidates with leading examples like Indinavir (Crixivan), Trandolapril (Mavik), Biyouyanagin A, endo pyrrolizidinone diastereomer [GSK] and several others. Domino reactions therefore constitute an integral part of both creative and functional aspects of drug design and discovery, contributing both enhanced efficiency as well as synthetic versatility to pharmaceutical drug design.

Novel domino reactions for diterpene synthesis.

New types of concerted domino acylation-cycloalkylation/alkylation-cycloacylation reactions have been described. These processes promoted by methanesulfonic acid-phosphorus pentoxide and concentrated H(2)SO(4), respectively, provide efficient, elegant, and expeditious routes for biologically active naturally occurring diterpenoids, namely (+/-)-ferruginol (1), (+/-)-nimbidiol (2), (+/-)-nimbiol (3), (+/-)-totarol (4), and ar-abietatriene (5).