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Design, Synthesis and In Vitro Evaluation of 2-Oxo-N-Substituted Phenyl- 2h-Chromene-3-Carboxamide Derivatives as Hiv Integrase Strand Transfer Inhibitors

[ Vol. 17 , Issue. 4 ]

Author(s):

Pankaj Wadhwa*, Priti Jain and Hemant R Jadhav   Pages 418 - 427 ( 10 )

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.

Keywords:

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

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



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