title: Enantiospecific Synthesis and Cytotoxicity Evaluation of Oximidine II Analogues.
abstract: Analogues of the anticancer natural product oximidine II were prepared and evaluated for cytotoxicity. One analogue of oximidine II that carries a C15 allylic amide side chain as well as two analogues with C15 vinyl sulfone side chains were found to lack cytotoxicity against the cancer cell line SK-Mel-5, thereby confirming the necessity of the C15 enamide side chain of oximidine II for cytotoxicity. Four analogues, designed by comparative molecular similarity index analysis (CoMSIA), that feature a less complex macrolactone scaffold were prepared and tested. The two analogues carrying a C15 vinyl sulfone group and the two analogues with a C15 oximidine II enamide side chain showed weak cytotoxicity against the SK-Mel-5 cell line and other cell lines, indicating that the designed simplified macrocycles cannot replace the oximidine II macrocycle.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS, 66045, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Schneider
authors.affiliation: Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN, 55414, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS, 66045, USA.
authors.forename: Kriangsak
authors.initials: K
authors.lastname: Khownium
authors.affiliation: Molecular Graphics & Modeling Laboratory, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS, 66045, USA.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Lushington
authors.affiliation: Department of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN, 55414, USA. Georg@umn.edu.
authors.forename: Gunda I
authors.identifier: 0000-0002-8900-9460
authors.initials: GI
authors.lastname: Georg
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D013237:Stereoisomerism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D007783:Lactones; C442267:oximidine II; D025262:Vacuolar Proton-Translocating ATPases
keywords: antitumor agents; benzolactone enamides; cytotoxicity; natural products; oximidines