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Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Design, Synthesis and In Vitro Evaluation of 2-Oxo-N-substituted Phenyl- 2H-chromene-3-carboxamide Derivatives as HIV Integrase Strand Transfer Inhibitors

Author(s): Pankaj Wadhwa*, Priti Jain and Hemant R. Jadhav

Volume 17, Issue 4, 2020

Page: [418 - 427] Pages: 10

DOI: 10.2174/1570180816666190617150803

Price: $65


Background: A series of eighteen 2-Oxo-N-substituted phenyl- 2H-chromene-3- carboxamide analogues has been evaluated for HIV-1 integrase (IN) inhibition.

Methods: The derivatives were synthesized via a two-step pathway commencing with 2- hydroxybenzaldehyde and diethyl malonate followed by hydrolysis of ester and coupling with various aromatic amines. The HIV-1 IN inhibitory potential of these compounds has been studied relative to dolutegravir, a known HIV-1 IN inhibitor using a standard available kit.

Results: Six molecules (compounds 13h, 13i, 13l, 13p to 13r) showed significant inhibition of HIV- 1 integrase 3′-strand transfer with IC50 values less than 1.7 μM. The presence of chromene-3- carboxamide motif was shown to be crucial for the enzymatic activity. In addition, molecular modelling studies were also done to justify the IN inhibition and in vitro-in silico correlation was drawn.

Conclusion: However, these compounds did not show HIV-1 and HIV-2 inhibition below their cytotoxic concentration indicating that these compounds cannot be taken further for anti-HIV activity as such and require structural modification.

Keywords: HIV-1 integrase, strand transfer, chromene-3-carboxamide, HIV-1 inhibition, cytotoxicity, Acquired immune deficiency syndrome (AIDS).

Graphical Abstract
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