Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug

Shaveta; Amrinder Singh; Matinder Kaur; Surbhi Sharma; Rajbir Bhatti; Palwinder Singh

doi:10.1016/j.ejmech.2014.03.003

Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: identification of a lead for anti-inflammatory drug

Eur J Med Chem. 2014 Apr 22:77:185-92. doi: 10.1016/j.ejmech.2014.03.003. Epub 2014 Mar 3.

Authors

Shaveta¹, Amrinder Singh¹, Matinder Kaur¹, Surbhi Sharma², Rajbir Bhatti², Palwinder Singh³

Affiliations

¹ Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India.
² Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India.
³ Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, Punjab 143005, India. Electronic address: palwinder_singh_2000@yahoo.com.

PMID: 24631898
DOI: 10.1016/j.ejmech.2014.03.003

Abstract

Conjugates of chromone-indole and chromone-pyrazole were screened for cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitory activities. Compounds 8 and 9 were identified as preferred inhibitors of COX-2 over the other two enzymes. Their IC50 for COX-2 was 29 nM and 20 nM, respectively and selectivity indices (SI) for COX-2 over COX-1 was 46 and 337. NMR, mass spectral studies and molecular modelling also indicated preferential interactions of compounds 8 and 9 with COX-2. Tested on albino mice against capsaicin induced algesia, compound 8 exhibited analgesic potential comparable to diclofenac. In addition to the biological profile, the desirable physico-chemical properties of these compounds make them promising leads for anti-inflammatory drugs.

Keywords: Chromone; Cyclooxygenase-2; Indole; Inhibitors; Interactions; Pyrazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Capsaicin
Chromones / chemistry*
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Cyclooxygenase Inhibitors / chemical synthesis
Cyclooxygenase Inhibitors / chemistry
Cyclooxygenase Inhibitors / pharmacology
Dose-Response Relationship, Drug
Drug Design*
Indoles / chemistry*
Mice
Models, Molecular
Molecular Structure
Pain / chemically induced
Pain / drug therapy*
Pain Measurement
Pyrazoles / chemistry*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Chromones
Cyclooxygenase Inhibitors
Indoles
Pyrazoles
pyrazole
indole
Cyclooxygenase 1
Cyclooxygenase 2
Capsaicin