Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B
| Autor: | Daisuke Yoshidome, Yukari Fujimoto, Koichi Fukase, Shinsuke Inuki, Emi Kashiwabara, Zenyu Shiokawa |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Scaffold Longamide B 01 natural sciences Biochemistry Piperazines Pyrrolopiperazinone 03 medical and health sciences Immune system Drug Discovery Indoleamine-Pyrrole 2 3 -Dioxygenase Pyrroles Enzyme Inhibitors General Pharmacology Toxicology and Pharmaceutics Indoleamine 2 3-dioxygenase Thioamide Pharmacology chemistry.chemical_classification 010405 organic chemistry Chemistry Alkaloid Organic Chemistry Matrix Attachment Regions 0104 chemical sciences Enzyme Activation 030104 developmental biology Docking (molecular) Pyrazoles Molecular Medicine |
| Zdroj: | ChemMedChem. 11:2682-2689 |
| ISSN: | 1860-7179 |
| DOI: | 10.1002/cmdc.201600446 |
| Popis: | Indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1-methyl-tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors. |
| Databáze: | OpenAIRE |
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