Synthesis of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage transformation

  • Eur J Med Chem. 2014 Mar 21:75:143-50. doi: 10.1016/j.ejmech.2013.12.053.
Malla Reddy Gannarapu  1 ,  Sathish Babu Vasamsetti  2 ,  Nagender Punna  1 ,  Naresh Kumar Royya  1 ,  Shanthan Rao Pamulaparthy  1 ,  Jagadeesh Babu Nanubolu  3 ,  Srigiridhar Kotamraju  4 ,  Narsaiah Banda  5
Affiliations
  • 1. Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
  • 2. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
  • 3. Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
  • 4. Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. Electronic address: [email protected].
  • 5. Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. Electronic address: [email protected].
PMID: 24531227 DOI: 10.1016/j.ejmech.2013.12.053
Abstract

A series of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives 7a-h and 9a-h were synthesized starting from sodium salt of saccharin 1 in series of steps. Final compounds 7a-h and 9a-h were evaluated for the anti-inflammatory activity and their ability to inhibit monocyte-to-macrophage transformation. Compounds 7e, 9b, 9e and 9h showed impressive anti-inflammatory activities (TNF-α, IL-8 and MCP-1) at micro molar concentration which was found to be better than positive control i.e., piroxicam. Compound 9e marginally and compound 9h significantly inhibited PMA-induced MMP-9 gelatinase activity. Also compounds 9e and 9h greatly inhibited the PMA-induced monocyte-to-macrophage transformation, a pre-requisite step in the formation of atheroma.

Keywords
Anti-inflammatory activity; N-aryl acetamide; Oxime ether; PMA-phorbol 12-myristate 13-acetate.