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
| Autor: | Wan Gang Gu, David Chi Cheong Wan, Sijie Liu, Xuan Zhang, Yan Wang, Yong-Tang Zheng, Joseph H. Chan, Denis Tsz-Ming Ip |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Stereochemistry medicine.medical_treatment Chromosomal translocation HIV Integrase Thiophenes Naphthalenes Toxicology Virus Replication Molecular Docking Simulation Small Molecule Libraries Inhibitory Concentration 50 Drug Delivery Systems Cell Line Tumor medicine Molecule Humans HIV Integrase Inhibitors biology Dose-Response Relationship Drug Growth factor General Medicine Small molecule Integrase medicine.anatomical_structure Viral replication biology.protein HIV-1 Intercellular Signaling Peptides and Proteins Nucleus |
| Zdroj: | Chemico-biological interactions. 213 |
| ISSN: | 1872-7786 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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