Antisickling potential of compounds derived from Detarium microcarpum (Fabaceae): in vitro and in silico studies

Autor: Olusola Olalekan Elekofehinti, Francis A. Obuseh, Merit E. Ayevbuomwan, Ehimwenma Sheena Omoregie
Rok vydání: 2020
Předmět:
Zdroj: Advances in Traditional Medicine. 21:725-737
ISSN: 2662-4060
2662-4052
DOI: 10.1007/s13596-020-00498-8
Popis: Detarium microcarpum is a legume tree of tropical Africa, widely known for its ethno-medicinal potentials. Previous studies have reported its rich contents of phytochemicals which could be linked to the bioactive principle of the plant. The in vitro antisickling properties of D. microcarpum stem bark was evaluated using blood samples obtained from thirty-five confirmed sickle cell disease patients using standard microscopic techniques. The research outcome showed that D. microcarpum extract inhibited sickling of red blood cells with a laudable mean difference compared to p-hydrozybenzoic acid (reference antisickling drug) which is a pure compound. To further expounds it’s mechanism of action, six compounds previously isolated from D. microcarpum stem bark and fruits was docked into the active sites of deoxy-hemoglobin (PDB ID: IGZX) and 2, 3-bisphosphoglycerate mutase (PDB ID: 1T8P) using Autodock Vina algorithm. Results from the in silico studies showed that oxokolavenic acid, 5α, 8α -2-oxokalavenic acid and Copalic acid exhibited the most favorable ligand–protein molecular interaction with deoxy-hemoglobin and 2,3-bisphosphoglycerate mutase when compared with the reference antisickling drug, hydroxyurea. The interaction of these compounds with deoxy-hemoglobin could alter hemoglobin conformation, favoring the relaxed state, thereby delaying/inhibiting hemoglobin polymerization and sickling. Their interactions with 2, 3-bisphosphoglycerate mutase could inhibit 2, 3-bisphosphoglycerate synthesis, thus delaying enhanced delivery of oxygen to tissues which is twice the case seen in sickle cell anemia. This clearly shows the possible mechanism of action of D. microcarpum and further substantiates the antisickling potential of these compounds derived from D. microcarpum leaves and fruits.
Databáze: OpenAIRE
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