Title:Design, Synthesis and In Vitro Evaluation of 2-Oxo-N-substituted Phenyl- 2H-chromene-3-carboxamide Derivatives as HIV Integrase Strand Transfer Inhibitors
Volume: 17
Issue: 4
Author(s): Pankaj Wadhwa*, Priti Jain and Hemant R. Jadhav
Affiliation:
- Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan,India
Keywords:
HIV-1 integrase, strand transfer, chromene-3-carboxamide, HIV-1 inhibition, cytotoxicity, Acquired immune deficiency
syndrome (AIDS).
Abstract:
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.
