Structure-Activity Analysis and Molecular Docking Studies of Coumarins from Toddalia asiatica as Multifunctional Agents for Alzheimer's Disease.

Coumarins, naturally occurring phytochemicals, display a wide spectrum of biological activities by acting on multiple targets. Herein, nine coumarins from the root of Toddalia asiatica were evaluated for activities related to pathogenesis of Alzheimer's disease (AD). They were examined for acetylcholinesterase (AChE) and AChE- or self-induced amyloid beta (Aß) aggregation inhibitory activities, as well as neuroprotection against H2O2- and Aß1-42-induced human neuroblastoma SH-SY5Y cell damage. Moreover, in order to understand the mechanism, the binding interactions between coumarins and their targets: (i) AChE and (ii) Aß1-42 peptide were investigated in silico. All coumarins exhibited mild to moderate AChE and self-induced Aß aggregation inhibitory actions. In addition, the coumarins substituted with the long alkyl chain at position 6 or 8 illustrated ability to inhibit AChE-induced Aß aggregation, resulting from their dual binding site at catalytic anionic site and peripheral active site in AChE. Moreover, the most potent multifunctional coumarin, phellopterin, could attenuate neuronal cell damage induced by H2O2 and Aß1-42 toxicity. Conclusively, seven out of nine coumarins were identified as multifunctional agents inhibiting the pathogenesis of AD. The structure-activity relationship information obtained might be applied for further optimization of coumarins into a useful drug which may combat AD.

Structural modification of 5,7-dimethoxyflavone from Kaempferia parviflora and biological activities.

5,7-Dimethoxyflavone, a major compound from Kaempferia parviflora, was used as a starting material for structural modification. Seven flavonoid derivatives have been synthesized from this flavone. Two new oxime derivatives 4 and 6 exhibited cytotoxicity against HepG2 cell line with IC50 values of 36.38 and 25.34 microg/mL, respectively, and against T47D cell line with IC50 values of 41.66 and 22.94 microg/mL, respectively. Compound 7 showed cytotoxicity against HepG2 and T47D cell lines with IC50 values of 21.36 and 25.00 microg/mL, respectively. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. In addition, oxime 6 exhibited antifungal activity against Candida albicans with an IC50 value of 48.98 microg/mL.