Design, Synthesis, and Conformation-Activity Study of Unnatural Bridged Bicyclic Depsipeptides as Highly Potent Hypoxia Inducible Factor-1 Inhibitors and Antitumor Agents.

A549 Cells Antineoplastic Agents / chemical synthesis Depsipeptides / chemical synthesis Drug Design Drug Screening Assays, Antitumor / methods HEK293 Cells HT29 Cells Humans Hypoxia-Inducible Factor 1 / antagonists & inhibitors MCF-7 Cells Structure-Activity Relationship

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
23 04 2020
Historique:
pubmed: 24 3 2020
medline: 25 9 2020
entrez: 24 3 2020
Statut: ppublish

Résumé

By carrying out structural modifications based on the bicyclic peptide structure of echinomycin, we successfully synthesized various powerful antitumor derivatives. The ring conformation in the obtained compounds was restricted by cross-linking with an unnatural bond. The prepared derivatives were demonstrated to strongly suppress the hypoxia inducible factor (HIF)-1 transcriptional activation and hypoxia induction of HIF-1 protein expression. Particularly, alkene-bridged derivative

Identifiants

DOI: 10.1021/acs.jmedchem.9b02039 PMID: 32202785
pubmed: 32202785
doi: 10.1021/acs.jmedchem.9b02039
doi:

Substances chimiques

Antineoplastic Agents 0
Depsipeptides 0
Hypoxia-Inducible Factor 1 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4022-4046

Auteurs

Kota Koike (K)

Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu-city, Gifu 501-1196, Japan.
ORCID: 0000-0003-3482-0747

Masanobu Nagano (M)

Department of Chemistry, The University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan.
ORCID: 0000-0002-2901-7610

Masahiro Ebihara (M)

Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, Gifu-city, Gifu 501-1193, Japan.
ORCID: 0000-0001-7183-326X

Tasuku Hirayama (T)

Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu-city, Gifu 501-1196, Japan.
ORCID: 0000-0003-4541-7849

Mieko Tsuji (M)

Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu-city, Gifu 501-1196, Japan.
ORCID: 0000-0003-2072-2118

Hiroaki Suga (H)

Department of Chemistry, The University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan.
ORCID: 0000-0002-5298-9186

Hideko Nagasawa (H)

Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu-city, Gifu 501-1196, Japan.
ORCID: 0000-0002-7662-0762

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules A549 › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Peptides cycliques › Depsipeptides › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Conception de médicament › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de criblage d'agents antitumoraux › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HT29 › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Facteur-1 induit par l'hypoxie › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Cellules MCF-7 › Design, Synthesis, and Conformation-Activity...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Design, Synthesis, and Conformation-Activity...