Abstract
Aim: Due to the complex nature of Alzheimer's disease, there is a renewed search for pleiotropic agents. Results: Purine+coumarin hybrids have been synthesized and tested for the potential treatment of Alzheimer's disease. Hybrids 6, 4a-b, 14c and 14e inhibit significantly soybean lipoxygenase, whereas derivatives 14b, c and 20a present antioxidative/lipoxygenase inhibition activities. Cholinesterase (ChE) and monoamino oxidase (MAO) inhibition studies have been carried out. Hybrid 20a is the most potent ChE inhibitor, in the low micromolar range, and selective for hBuChE (IC50 = 4.65 ± 0.23 μM), whereas hybrid 14a is the most potent MAOI, in the low micromolar range, and selective for MAO-B (IC50 = 6.8 ± 0.6 μM). Conclusion: The preliminary experimental results point to two selective multitarget lead compounds 20a and 4b.
Acknowledgement
The authors are grateful to A Leo and Biobyte for free access.
Financial & competing interests disclosure
J Marco-Contelles thanks MINECO (SAF2012–33304)//Universidad Camilo José Cela (MULTIMOL 2013–20; TANOTOX 2013–21) for support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.