title: Examining the structure-activity relationship of benzopyran-based inhibitors of the hypoxia inducible factor-1 pathway.
abstract: Many forms of solid tumor have a characteristic feature known as hypoxia, which describes a low or non-existent presence of oxygen in the cellular microenvironment. This decrease in oxygen causes activation of the hypoxia inducible factor (HIF) pathway, which activates the transcription of many genes that cause cell proliferation, metastasis, increased glycolysis and angiogenesis. Increased HIF expression has been linked with poor patient prognosis, increased malignancy, and therapeutic resistance. Previous work in our lab has identified 1 and 2 as inhibitors of the HIF pathway, specifically as disrupters of the p300-HIF-1α complex formation. A library of sulfonamide analogs has been designed and synthesized with the intent of examining the SAR of this series of compounds and improving potency and physicochemical properties as compared with lead compounds 1 and 2. At the end, we have achieved a thorough understanding of the structural features critical for future optimization work.
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Jalisa
authors.initials: J
authors.lastname: Ferguson
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Zeus
authors.initials: Z
authors.lastname: De Los Santos
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Narra
authors.initials: N
authors.lastname: Devi
authors.affiliation: Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Erwin
authors.initials: E
authors.lastname: Van Meir
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Department of Chemistry and Physics, Armstrong State University, Savannah, GA 31419, USA. Electronic address: sarah.zingales@armstrong.edu.
authors.forename: Sarah
authors.initials: S
authors.lastname: Zingales
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA. Electronic address: wang@gsu.edu.
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: Hypoxia inducible factor inhibitors; Molecular docking; Structure-activity relationship