Synthesis, pharmacological activities and molecular docking studies of pyrazolyltriazoles as anti-bacterial and anti-inflammatory agents

  • Bioorg Med Chem. 2017 Oct 15;25(20):5678-5691. doi: 10.1016/j.bmc.2017.08.042.
Cherupally Dayakar  1 ,  Buddana Sudheer Kumar  2 ,  Galande Sneha  2 ,  Gudem Sagarika  3 ,  Koneru Meghana  3 ,  Sistla Ramakrishna  3 ,  Reddy Shetty Prakasham  2 ,  Bhimapaka China Raju  4
Affiliations
  • 1. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 2. Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 3. Pharmacology and Toxicology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
  • 4. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: [email protected].
PMID: 28927905 DOI: 10.1016/j.bmc.2017.08.042
Abstract

A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81µg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC50 6.23μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α.

Keywords
1H-Pyrazole-4-carbaldehydes; Anti-bacterial activity; Anti-inflammatory activity; Pyrazolyl-1H-1,2,3-triazoles; Pyrazolyl-1H-1,2,3-triazolyl alcohols; Pyrazolyl-1H-1,2,3-triazolylcarboxylates.