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Research Article

Alizarin interaction with sickle hemoglobin: elucidation of their anti-sickling properties by multi-spectroscopic and molecular modeling techniques

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Pages 4614-4631 | Received 14 Aug 2018, Accepted 06 Dec 2018, Published online: 24 Jan 2019
 

Abstract

Polymerization of hemoglobin S is a major cause of morbidity and mortality in sickle cell disease, which leads to sickling and destruction of red blood cell. Alizarin, a bioactive compound from Rubia cordifolia, is reported to be blood purifier. This study investigates the potential of alizarin as an anti-sickling agent, showing a significant decrease in the rate of polymerization, therefore inhibiting the rate of sickling with increasing concentration. Interaction studies indicated that the fluorescence intensity of sickle hemoglobin (Hb S) decreases gradually with increasing alizarin concentration. This suggests the static quenching, where binding constant and the number of binding sites were deduced at different temperatures. The negative values of Gibbs energy change (ΔG0) strongly suggest that it is entropy-driven spontaneous and exothermic reaction. Negative enthalpy (ΔH0) and positive entropy (ΔS0) stipulated that hydrogen and hydrophobic bonding forces were interfering in a hydrophobic micro-environment of β6Val leading to Hb S polymerization inhibition. In circular dichroism (CD) spectra, Hb S in the presence of alizarin shows helical structural changes leading to destabilization of Hb S polymer. These findings were also supported by molecular docking simulation studies using DOCK6 and GROMACS. So, from these findings, we may conclude that alizarin interacts with Hb S through hydrogen bonding and leading to inhibition of Hb S polymerization. Consequently, alizarin may have potential use as an anti-sickle cell medication for sickle cell disorder.

Communicated by Ramaswamy H. Sarma

Acknowledgements

The authors are indebted to the central instrumentation facility of the Savitribai Phule Pune University, Pune. We are also grateful to all the authorities of the Sickle Cell Unit, Sane Guruji Hospital, MAM’s Sumatibhai Shah Ayurved Mahavidyalaya, Pune, and sickle cell patients who agreed to provide their blood for this research.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This research was supported by Grant DST-SERB [GOI A-738] and partially supported by DIC MHRD GOI.

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