1,4-Bis(5-(naphthalen-1-yl)thiophen-2-yl)naphthalene, a small molecule, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular Lens epithelium-derived growth factor

Wan Gang Gu, Denis Tsz Ming Ip, Si Jie Liu, Joseph H. Chan, Yan Wang, Xuan Zhang, Yong Tang Zheng, David Chi Cheong Wan

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Translocation of viral integrase (IN) into the nucleus is a critical precondition of integration during the life cycle of HIV, a causative agent of Acquired Immunodeficiency Syndromes (AIDS). As the first discovered cellular factor to interact with IN, Lens epithelium-derived growth factor (LEDGF/p75) plays an important role in the process of integration. Disruption of the LEDGF/p75-IN interaction has provided a great interest for anti-HIV agent discovery. In this work, we reported that one small molecular compound, 1,4-bis(5-(naphthalen-1-yl)thiophen-2-yl)naphthalene(Compound 15), potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution at 1 μM. The putative binding mode of Compound 15 was constructed by a molecular docking simulation to provide structural insights into the ligand-binding mechanism. Compound 15 suppressed viral replication by measuring p24 antigen production in HIV-1IIIB acute infected C8166 cells with EC50 value of 11.19 μM. Compound 15 might supply useful structural information for further anti-HIV agent discovery.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalChemico-Biological Interactions
Volume213
Issue number1
DOIs
StatePublished - Apr 25 2014

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Keywords

  • HIV-1 integrase
  • Lens epithelium-derived growth factor (LEDGF/P75)
  • Molecular docking

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