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

• Published in: Frontiers in chemistry Vol. 9; p. 711190
• Main Authors: Alamzeb, Muhammad, Setzer, William N, Ali, Saqib, Khan, Behramand, Rashid, Mamoon-Ur, Ihsanullah, Salman, Syed Muhammad, Adnan, Omer, Muhammad, Ali, Javed, Ullah, Asad
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17-12-2021
• Subjects: Berberis glaucocarpa; bioassay studies 3; bisbenzylisoquinoline; Chemistry; chondrofolinol; molecular docking; chondrofolinol; bisbenzylisoquinoline; molecular docking; bioassay studies 3; Berberis glaucocarpa
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2021.711190

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.