GC-MS aided In silico molecular docking studies on the anti-sickling properties of Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler stem bark

Abstract

Zanthoxylum zanthoxyloides is an important medicinal herb in African traditional medicine. It has been used to treat an array of pathological conditions, most notably is sickle cell anaemia, one of the most important genetic haematological conditions affecting individuals of African descent. This study identifies and evaluates Zanthoxylum zanthoxyloides bioactives with potential haemoglobin oxygen-affinity modulatory activity. Phytochemical constituents identified via gas chromatography-mass spectrometry of a 70% ethanolic stem bark extract of Zanthoxylum zanthoxyloides (Lam.) Zepern. and Timler were analyzed for their in silico anti-sickling activity. Gas chromatography-mass spectrometry aided in silico molecular docking studies identified the presence of two compounds, 7-(dimethylamino)-2,3-dihydro-1H cyclopenta[c]chromen-4-one and (8S,9S,10R,13S,14S,16R,17S)-17-acetyl-6,10,13,16-tetramethyl-8,9,11,12,14,15,16,17-octahydrocyclopenta[a]phenanthren-3-one, with a strong binding affinity for the active pocket located at the N-terminal region (valine 1) of the alpha globin subunit of haemoglobin S. Further analysis of the binding pose of the ligands demonstrated the formation of favourable interactions including hydrogen bonding, π-cation, van der Waals and hydrophobic contacts. Computational investigations on the pharmacokinetic profile of 7-(dimethylamino)-2,3-dihydro-1H cyclopenta[c]chromen-4-one and (8S,9S,10R,13S,14S,16R,17S)-17-acetyl-6,10,13,16-tetramethyl-8,9,11,12,14,15,16,17-octahydrocyclopenta[a]phenanthren-3-one reveals a favourable oral bioavailability and drug-likeness profile. The findings add to the evidence bolstering the role of Zanthoxylum zanthoxyloides in the management of sickle cell anemia.