2. Academic Validation
  3. Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis

Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis

  • Eur J Med Chem. 2017 Apr 21:130:223-239. doi: 10.1016/j.ejmech.2017.02.052.
Jitender Dev G 1,  Y Poornachandra 2,  K Ratnakar Reddy 1,  R Naresh Kumar 1,  N Ravikumar 3,  D Krishna Swaroop 1,  P Ranjithreddy 4,  G Shravan Kumar 5,  Jagadeesh B Nanubolu 6,  C Ganesh Kumar 2,  B Narsaiah 7
Affiliations

Affiliations

  • 1 Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
  • 2 Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
  • 3 Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Department of Chemistry, Osmania University, Tarnaka, Hyderabad, 500007, India.
  • 4 Department of Chemistry, Osmania University, Tarnaka, Hyderabad, 500007, India.
  • 5 Bioinformatics Division, Osmania University, Hyderabad, 500007, India.
  • 6 Laboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India.
  • 7 Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, India. Electronic address: narsaiah@iict.res.in.
PMID: 28254697 DOI: 10.1016/j.ejmech.2017.02.052
Abstract

A series of novel alkyl amide functionalized 2,3-pyrazole fused quinoline derivatives 5, 6 and 7 have been prepared starting from quinoline-2(1H)one 1 in a series of steps. All the final products were screened for Antibacterial activity, the promising lead compound 5r was identified with MIC values ranging between 3.9 and 7.8 μg/mL against different Bacterial strains. Compound 5r also showed good Antifungal and anti-biofilm activities against the tested panel of various Fungal and Bacterial strains. Compound 5r when treated on mature biofilms of S. aureus strain MLS16, showed increased levels of intracellular ROS accumulation suggesting its contribution to the bactericidal activity. All the compounds were also screened for Anticancer activity against a panel of four human Cancer cell lines. Based on these studies, compounds 5c, 5d, 5r and 7f were considered as promising and exhibited significant cytotoxicity with IC50 values of <15 μM. The biological activity data was further validated by molecular modeling and CoMFA studies.

Keywords

Anticancer activity; Antimicrobial activity; Chlorination; Pyrazole fused quinoline; Quinoline 2(1H) one.

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