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Synthesis and Evaluation of 3-(1,3-dioxoisoindolin-2-yl)-N-substituted Phenyl Benzamide Analogues as HIV Integrase Strand Transfer Inhibitors

[ Vol. 17 , Issue. 2 ]

Author(s):

Pankaj Wadhwa*, Priti Jain, Arpit Patel, Shantanu Shinde and Hemant R. Jadhav   Pages 105 - 114 ( 10 )

Abstract:


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.

Keywords:

HIV-1 integrase, strand transfer inhibitors, N-substituted phenyl benzamide, AIDS, IN inhibitors, docking studies.

Affiliation:

Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan

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