title: Synthesis and Antiproliferative Activity Evaluation of the Disulfide-Containing Cyclic Peptide Thiochondrilline C and Derivatives.
abstract: Thiochondrilline C (4) was previously isolated from Verrucisispora sp. and reported to have moderate cytotoxicity against human lung adenocarcinoma cells. Herein, we report the synthesis of thiochondrilline C by N-terminal peptide extension, oxidative disulfide bond formation, and heterocycle installation as key steps. Antiproliferative activities for the prepared natural product and several derivatives against the NCI 60 cancer cell line panel are also described. Derivative 22 was identified as a moderately potent antiproliferative agent (50% growth inhibition (GI50) = 0.2-12.2 μM) with leukemia (average GI50 = 1.8 ± 0.1 μM) and colon (average GI50 = 2.4 ± 0.3 μM) cells being most sensitive.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
authors.forename: Mohana Rao
authors.initials: MR
authors.lastname: Vippila
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
authors.forename: Phuong Kim
authors.initials: PK
authors.lastname: Ly
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Cuny
mesh_terms: D000230:Adenocarcinoma; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D004220:Disulfides; D010455:Peptides; C050632:polypeptide C; C000604764:thiochondrilline C