Premium
Pyridyl Derivatives of Benzaldehyde as Potential Antisickling Agents
Author(s) -
Nnamani Ijeoma N.,
Joshi Gajanan S.,
DansoDanquah Richmond,
Abdulmalik Osheiza,
Asakura Toshio,
Abraham Donald J.,
Safo Martin K.
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890165
Subject(s) - chemistry , aldehyde , allosteric regulation , substituent , stereochemistry , vanillin , pyridoxal , adduct , schiff base , benzaldehyde , biochemistry , organic chemistry , receptor , enzyme , catalysis
Compounds that bind to sickle hemoglobin (Hb S) producing an allosteric shift to the high‐affinity Hb S that does not polymerize are being developed to treat sickle cell anemia (SCA). In this study, three series of pyridyl derivatives of substituted benzaldehydes (Classes I–III) that combine structural features of two previously determined potent antisickling agents, vanillin and pyridoxal, were synthesized. When analyzed with normal human whole blood, the compounds form Schiff ‐base adducts with Hb and left shift the oxygen equilibrium curve (OEC) to the more soluble high‐affinity Hb, more than vanillin or pyridoxal. Generally, Class‐I compounds with an aromatic aldehyde located ortho to the pyridyl substituent are the most potent, followed by the Class‐II compounds with the aldehyde at the meta ‐position. Class‐III compounds with the aldehyde at the para position show the weakest activity. The structure–activity studies of these pyridyl derivatives of substituted benzaldehydes demonstrate significant allosteric potency that may be useful for treating SCA.