Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction

Abstract

Objectives: Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses. Therefore, to find potential compounds that could be developed as novel HNMT inhibitors, this study conducted an in silico study of the secondary metabolites of Nigella sativa L and Curcuma xanthorrhiza Roxb.

Methods: In this study, we conducted a molecular docking study of 36 secondary metabolites of N. sativa L and 26 secondary metabolites of C. xanthorrhiza Roxb using an in silico approach targeting HNMT protein (PDB ID: 2AOT) using AutoDockVina software. The prediction of ADMET characteristics was done using the pkCSM Online Tool.

Results: This study obtained one metabolite from N. sativa L (longifolene) and seven metabolites from C. xanthorrhiza Roxb {(+)-beta-atlantone, humulene epoxide, (-)-beta-curcumene, (E)-caryophyllene, germacrone, (R)-(-)-xanthorrhizol, and (-)-beta-caryophyllene epoxide} which were predicted to have potential to be developed as HNMT inhibitors.

Conclusions: This study found several secondary metabolites of N. sativa L and C. xanthorrhiza Roxb which had activity as HNMT inhibitors. This research can likewise be utilized as a basis for further research, both in vitro, in vivo, and clinical trials related to the development of secondary metabolites from N. sativa L and C. xanthorrhiza Roxb as novel HNMT inhibitor compounds.

Keywords: Curcuma xanthorrhiza; HNMT inhibitor; Nigella sativa; in silico studies; mental illness.