Organometal-catalytic reactions have been extensively used for organic synthesis. For example, the palladium-catalytic C-C bond formation, copper-catalytic C-N bond formation, and magnesium-mediated C-C bond construction, they all are suitable to the transformation of functionalities and the production of derivatives/analogues. We will utilize the related organometallic reaction to systematically buildup a variety of heterocyclic-based anticancer agents, including (1) 5-aryl/heteroaryl/alkynyl/hydroxyl/cyano/amide-quinolines and 2- or 4-aryltrimethoxyquinolines (Specific aim 1), (2) N1-aryl/heteroaryl and C3-aryl/heteraryl-5,6,7-trimethoxyindoles (Specific aim 2), (3) 2-Aryl-pyridinyl (phenyl)-3-benzenesulfonamides (Specific aim 3), and (4) 4-aryl/heteroaryl/alkynyl/alkenyl/hydroxyl/cyano/amide-5-methoxy-1- and 2-aroylindoles (Specific aim 4). In our preliminary data for antiproliferative activity against cervical human cancer cell line KB, compounds 8-996-2, 8-905, 12-186-B, and 95-68-A showed substantial cell growth inhibitory activities with IC50 values of 37.5, 2.8, 13.7, and 150 nM, respectively. On the basis of results above, we will further design and synthesize more compounds for the research of structure-activity relationship. The selected potential compounds will be studied their mode of actions in cancer, and evaluated their antitumor activity in vivo human xenograft modes bearing human cancer cell lines.
|Effective start/end date||8/1/13 → 7/31/14|