Interaction of Antimalarial Drug, Pyrimethamine and Sulphadoxine with Sickle Haemoglobin at pH 5.0 and pH 7.2: A Fourier Transform Infrared (FTIR) Study

Aggregation of sickle haemoglobin (HbS), upon deoxygenation, is responsible for an inherited genetic disorder in the human red blood cells (RBCs) known as Sickle cell disease (SCD). On the suggestion that this phenomenon could arise from some form of conformational changes in the structure of HbS arising from a pH-induced rearrangement of secondary structural elements of the haemoglobin, Fourier Transform Infrared (FTIR) spectroscopy (in the mid-infrared region) was used to measure the amino acid side chain absorbance and also, the secondary structural transitions in the protein. A comparative study between the interaction of HbS with Pyrimethamine and sulphadoxine at pH 5.0, (the acidic pH of malarial parasites’ digestive vacuole during the intra-erythrocytic development and proliferation), and the body’s physiological pH of 7.2 was carried out. The amide I region (1700 – 1600 cm-1) comprising the amino acids side-chains absorbance and the proteins secondary structural components (α-helix, β-sheets, random and turn structures) showed that at pH 5.0 for Pyrimethamine-sulphadoxine combination therapy, there were significant changes in absorbance for HbS while at pH 7.2, little or no significant absorbance changes were observed. The results suggest that HbS is easily destabilized at pH 5.0 than pH 7.2 on interaction with Pyrimethamine and sulphadoxine. These interactions may hinder the development of the Plasmodium falciparum at the intra-erythrocytic stage and may account for the novel strategies of monitoring HbS aggregation during malarial infection as well as improvements in administering effective antimalarial treatment.