Synthesis and serum protein binding of novel ring-substituted harmine derivatives

摘要: A series of new derivatives the natural β-carboline alkaloid harmine, introducing hydrophobic substituents into positions 7 and 9 were synthesized as potential anticancer agents. Their binding affinities for human serum albumin (HSA) α1-acid glycoprotein (AAG) investigated by affinity chromatography combined with fluorescence, circular dichroism (CD) UV absorption spectroscopy. The weak harmine to both proteins (Ka ∼ 3 × 104 M−1) was highly increased aromatic substitutions 105–106 M−1). Derivatives having a substituted benzyl group in N9-position nucleus showed about tenfold hundredfold enhancement HSA AAG, respectively. Such strong plasma protein interaction would be pharmacokinetic relevance these drug candidates. Induced CD spectra indicated variant selective, dimeric 7-pyridylethoxy derivative AAG. Absorbance fluorescence refer preference neutral form studied β-carbolines proteins.