title: Synthesis and cytotoxicity studies of Hedgehog enzyme inhibitors SANT-1 and GANT-61 as anticancer agents.
abstract: Cancer-related death is one of the most common causes of mortality in society. Small molecules have the capability to disrupt aberrant signaling pathways in tumors, leading to anticancer activities. Therefore the search for new molecules for cancer treatment continues to draw attention to the scientific research community. Synthesis and biological evaluation of hedgehog (Hh) pathway inhibitors SANT-1 and GANT-61 are disclosed. These molecules have been synthesized from common precursors using simple conversions, our synthesis features Vils-Meier-Haack reaction, imine formation reaction and N-arylation reaction. These drugs were evaluated using a Hh reporter assay to confirm pathway inhibitory activity, and tested for cell viability against pancreatic and prostate cancer cells. These methodologies can be applied to make potent analogs of both inhibitors.
authors: a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , Maryland , USA.
authors: Venugopal
authors: V
authors: Chenna
authors: Chaoxin
authors: C
authors: Hu
authors: Saeed R
authors: SR
authors: Khan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C551027:GANT 61; D053823:Hedgehog Proteins; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C468919:SANT-1 compound