Biochemical investigation of the upstream anti-sickling mechanisms of soursop (): 15-acetyl guanacone as an inhibitor of deoxyhaemoglobin polymerisation.

Current sickle cell disease (SCD) therapies are limited and inefficient. The ethnomedicinal values of in the treatment of SCD, leading to this present research. Leaves and fruits of were processed using solvent extraction and partitioning; aqueous, chloroform and ethyl acetate fractions. (anti-oxidant and anti-sickling), quantitative (amino acids) and kinetic simulation experiments were done. 15-acetyl guanacone, was used, against 2,3-bisphosphoglycerate (2, 3-BPG) mutase and deoxyhaemoglobin. The ethyl acetate and chloroform fractions better NO scavengers, iron-chelators and ferric reducing. unsickling () had ethyl acetate = 5 h and methanol = 7 h. Chloroform fraction had 1.00 mg/mL ( = 546 mg/mL) to 10.00 mg/mL ( = 99 mg/mL). and of ethyl acetate fraction had steady-decrease. At higher concentration, chloroform fraction had higher (1.48 × 10 U/mL) and higher (3.66 × 10 mg/mL), whereas, at a lower concentration, the ethyl acetate fraction demonstrated higher (7.23 × 10 U/mL) and lower (2.12 × 10 mg/mL); The relative affinity () of chloroform fraction increased progressively with concentration. The amino acid profile revealed rich concentrations glycine, valine, leucine, lysine, phenylalanine, histidine, arginine, and tryptophan. From the experiments, 15-acetyl guanacone specifically targeted the A and B chains, with greater affinity for the beta subunit. This suggested that 15-acetyl guanacone might be able to prevent the polymerisation of deoxyHbSS, induce an allosteric conformational change that increases the oxygen affinity, and decrease the cellular 2, 3-BPG concentration.Communicated by Ramaswamy H. Sarma.