AUTHOR=Alamzeb Muhammad , Setzer William N. , Ali Saqib , Khan Behramand , Rashid Mamoon-Ur- , Ihsanullah  , Salman Syed Muhammad , Adnan  , Omer Muhammad , Ali Javed , Ullah Asad 

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

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.711190

DOI=10.3389/fchem.2021.711190

ISSN=2296-2646

ABSTRACT=<p>A new bisbenzylisoquinoline named as chondrofolinol <bold>(1)</bold> and four reported compounds <bold>(2–5)</bold> were isolated and characterized from the roots of <italic>Berberis glaucocarpa</italic> Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of <italic>Leishmania tropica</italic>, 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 <italic>Leishmania tropica</italic>. 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 <italic>Leishmania</italic>. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of <italic>N</italic>-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for <italic>Leishmania major</italic> were selected after thorough literature search about protein targets responsible for inflammation and <italic>Leishmania major.</italic> Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The <italic>Leishmania major</italic> 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.</p>