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

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

doi:10.3389/fchem.2021.711190

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

Front Chem. 2021 Dec 17:9:711190. doi: 10.3389/fchem.2021.711190. eCollection 2021.

Authors

Affiliations

¹ Department of Chemistry, University of Kotli, Kotli, Pakistan.
² Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL , United States.
³ Department of Chemistry, Islamia College University, Peshawar, Pakistan.
⁴ Department of Chemistry, Baluchistan University of Information Technology, Engineering and Management Sciences (BUITEMS), Takatu Campus, Quetta, Pakistan.
⁵ Institute of Chemical Sciences, University of Swat, Swat, Pakistan.
⁶ Department of Chemistry, Kohat University of Science and Technology (KUST), Kohat, Pakistan.

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 anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major 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.

Keywords: Berberis glaucocarpa; bioassay studies 3; bisbenzylisoquinoline; chondrofolinol; molecular docking.