A number of substituted benzaldehydes, notably 12C79 (also known as BW12C or valerosol) and 589C80 (BWA589C or tucaresol),were also designed to act in a similar manner but with greater binding ability to Hb. In experiments involving cyclical deoxygenation and reoxygenation of sickle cells in vitro bothwere effective in maintaining intracellular
K+, high MCV and better deformability. Combination of these benzaldehydes to act via reducing HbS depolymerisation along with direct inhibition of the Gardos channel with clotrimazole and nitrendipine was synergistic in protecting sickle RBCs from shrinkage and K+ loss during episodes of cyclical deoxygenation. In clinical trials, 12C79 (valerosol) was effective in increasing O2 affinity of Hb both in normal HbAA individuals [37] and SCD patients [38] but had a rather short half life. Although 589C80 (tucaresol) with its longer half life and ability to improve haematological parameters in sickle patients, side-effects included fever and cervical lymphadenopathy