Design, Synthesis, and Molecular Docking Analysis of Fluorinated MLN4924 Derivatives as Antiviral Agents

Kisu Sung, Seokhwan Hyeon, Minjae Kim, Pramod K. Sahu, Siddhi D. Naik, Vikas R. Aswar, Sushil K. Tripathi, Tong Shin Chang, Jin Hyun Ahn, Jinha Yu, Lak Shin Jeong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

MLN4924 is known for its potential in cancer treatment and antiviral activity as a NEDD8-activating enzyme (NAE) inhibitor. We designed and synthesized fluorinated MLN4924 derivatives by electrophilic fluorination at the 6′-position and nucleophilic fluorination at the 2′-position of the sugar moiety, respectively. The compounds were then evaluated for their anti-HCMV activity, and compound 2 a exhibited the most potent HCMV inhibitory activity, showing similar results to MLN4924 but with no toxicity at a high concentration. Docking studies highlighted the importance of the sugar conformation in the binding interaction with the target protein. This research offers critical insights into the optimization of MLN4924 derivatives and provides a promising pathway towards the development of effective antiviral agents.

Original languageEnglish
Article numbere202300416
JournalAsian Journal of Organic Chemistry
Volume12
Issue number11
DOIs
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • Antiviral
  • Docking studies
  • Fluorination
  • Inhibitors
  • MLN4924

Fingerprint

Dive into the research topics of 'Design, Synthesis, and Molecular Docking Analysis of Fluorinated MLN4924 Derivatives as Antiviral Agents'. Together they form a unique fingerprint.

Cite this