Vanillin, a potential agent for the treatment of sickle cell anemia

Author(s): Abraham DJ, Mehanna AS, Wireko FC, Whitney J, Thomas RP, et al.


Vanillin, a food additive, has been evaluated as a potential agent to treat sickle cell anemia. Earlier studies indicated that vanillin had moderate antisickling activity when compared with other aldehydes. We have determined by high performance liquid chromatography that vanillin reacts covalently with sickle hemoglobin (HbS) both in solution and in intact red blood cells. Hemoscan oxygen equilibrium curves show a dose-dependent left shift, particularly at low oxygen tensions. Rheologic evaluation (pO2 scan Ektacytometry) of vanillin-reacted HbS erythrocytes shows a dose-dependent inhibition of deoxygenation-induced cell sickling. Ektacytometry also suggests that vanillin may have a direct inhibitory effect on HbS polymer formation. Vanillin has no adverse effects on cell ion or water content. X-ray crystallographic studies with deoxyhemoglobin (HbA)-vanillin demonstrate that vanillin binds near His 103 alpha, Cys 104 alpha, and Gln 131 beta in the central water cavity. A secondary binding site is located between His 116 beta and His 117 beta. His 116 beta has been implicated as a polymer contact residue. Oxygen equilibrium, ektacytometry, and x-ray studies indicate that vanillin may be acting to decrease HbS polymerization by a dual mechanism of action; allosteric modulation to a high-affinity HbS molecule and by stereospecific inhibition of T state HbS polymerization. Because vanillin is a food additive on the GRAS (generally regarded as safe) list, and because it has little or no adverse effects at high dosages in animals, vanillin is a candidate for further evaluation as an agent for the treatment of sickle cell disease.

Similar Articles

In vitro antisickling activities and phytochemical evaluation of Plumbagozeylanica and Uvariachamae

Author(s): Olufunmilayo EA, Adelodun LK, Oladimeji PR, Lateef SK

Sickle cell disease in Africa

Author(s): Diallo D, Tchernia G

A Comprehensive Review on Biological Activities of P-Hydroxy Benzoic Acid and Its Derivatives

Author(s): RohiniManuja, ShikhaSachdeva, Akash Jain, Jasmine Chaudhary

Schiff base adducts of hemoglobin

Author(s): Zaugg RH, Walder JA, Klotz IM

Chromatographic analysis of antisickling compounds in Zanthoxylum species

Author(s): Elujoba AA, Nagels L, Sofowora A, VanDongen W

Alternative aspirins as antisickling agents: acetyl-3,5-dibromosalicylic acid

Author(s): Walder JA, Zaugg RH, Iwaoka RS, Watkin WG, Klotz IM

NMR study of the sites of human hemoglobin acetylated by aspirin

Author(s): Xu AS, Macdonald JM, Labotka RJ, London RE

Design, synthesis, and testing of potential antisickling agents

Author(s): Abraham DJ, Gazze DM, Kennedy PE, Mokotoff M

Antisickling properties of divanilloylquinic acids isolated from Fagarazanthoxyloides Lam

Author(s): Ouattara B, Jansen O, Angenot L, Guissou IP, Frédérich M, et al.