DataSheet1.PDF

Abstract

A new bisbenzylisoquinoline named as Chondrofolinol (1) and four reported compounds (2-5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic and leishmanicidal studies were performed against carrageenan induced paw edema, yeast induced pyrexia and the promastigotes of Leishmania tropica respectively. The new compound significantly reduced the paw volume in carrageenan induced paw edema and rectal temperature in yeast induced pyrexia at 10 and 20 mg/Kg of body weight. Chondrofolinol caused almost 100 % inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and antileishmanial activities, a molecular docking study was carried out on relevant human protein targets of inflammation and Leishmania. Chondrofolinol showed strong docking to human endoplasmic reticulum aminopeptidase 2 (Hs ERAP2) and to human matrix metalloproteinase-1 (Hs MMP-1). The Leishmania protein targets with the most exothermic docking energies to chondrofolinol were L. major N-myristoyltransferase (Lmaj NMT), L. major tyrosyl-tRNA synthetase (Lmaj TyrRS), and L. major uridine diphosphate-glucose pyrophosphorylase (Lmaj UGPase). The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.