Synthesis and bio-evaluation of alkylaminoaryl phenyl cyclopropyl methanones as antitubercular and antimalarial agents

Arya Ajay, Vandana Singh, Shubhra Singh, Swaroop Pandey, Sarika Gunjan, Divya Dubey, Sudhir Kumar Sinha, Bhupendra N. Singh, Vinita Chaturvedi, Renu Tripathi, Ravishankar Ramchandran, Rama P. Tripathi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a-6u and 8a-8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d-6h, 6p, 6q and 8a-8c) exhibited good in vitro antitubercular activities with MIC values 3.12-12.5 μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a-6d, 6f, 6s, 8a and 8c) with IC50 as low as 0.080 and 0.035 μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25 μM concentration of the compound.

Original languageEnglish
Pages (from-to)8289-8301
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number23
DOIs
StatePublished - 1 Dec 2010
Externally publishedYes

Keywords

  • Antimalarial
  • Antitubercular
  • Cyclopropylphenyl methanones
  • FAS-II
  • Mycobacterium tuberculosis H37Rv
  • Plasmodium falciparum 3D7

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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