Synthesis and Evaluation of 3-(1,3-dioxoisoindolin-2-yl)-N-substituted Phenyl Benzamide Analogues as HIV Integrase Strand Transfer Inhibitors
| Autor: | Shantanu D. Shinde, Arpit Patel, Hemant R. Jadhav, Pankaj Wadhwa, Priti Jain |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
biology 010405 organic chemistry Stereochemistry Chemistry 01 natural sciences 0104 chemical sciences Strand transfer Integrase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Infectious Diseases biology.protein 030212 general & internal medicine Benzamide |
| Zdroj: | Anti-Infective Agents. 17:105-114 |
| ISSN: | 2211-3525 |
| DOI: | 10.2174/2211352516666181102121920 |
| Popis: | Background: A series of novel 3-(1,3-dioxoisoindolin-2-yl)-N-substituted phenyl benzamide derivatives was synthesized and tested in vitro against human immunodeficiency virus type-1 Integrase (HIV-1 IN). Methods: Out of the 18 analogues, six (compounds 16c, 16h, 16i, 16m, 16n and 16r) showed significant inhibition of strand transfer by HIV-1 integrase. For these six compounds. IC50 was below 5.0 µM. In silico docking studies revealed that the presence of 2-phenyl isoindoline-1,3-dione motif was essential as it was found to interact with active site magnesium. Results: To further confirm the results, cell-based HIV-1 and HIV-2 inhibitory assay was carried out. Conclusion: These compounds possess structural features not seen in previously reported HIV-1 integrase inhibitors and thus can help further optimization of anti-HIV-1 integrase activity. |
| Databáze: | OpenAIRE |
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