Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid.

A new bisbenzylisoquinoline named as chondrofolinol and four reported compounds were isolated and characterized from the roots of Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of , 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 . 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 anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and . Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of -myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for were selected after thorough literature search about protein targets responsible for inflammation and Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and 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.