1548331-34-5Relevant academic research and scientific papers
Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease
Bisceglia, Federica,Seghetti, Francesca,Serra, Massimo,Zusso, Morena,Gervasoni, Silvia,Verga, Laura,Vistoli, Giulio,Lanni, Cristina,Catanzaro, Michele,De Lorenzi, Ersilia,Belluti, Federica
, p. 1420 - 1433 (2019/01/11)
Alzheimer's disease is likely to be caused by copathogenic factors including aggregation of Aβ peptides into oligomers and fibrils, neuroinflammation, and oxidative stress. To date, no effective treatments are available, and because of the multifactorial nature of the disease, it emerges the need to act on different and simultaneous fronts. Despite the multiple biological activities ascribed to curcumin as neuroprotector, its poor bioavailability and toxicity limit the success in clinical outcomes. To tackle Alzheimer's disease on these aspects, the curcumin template was suitably modified and a small set of analogues was attained. In particular, derivative 1 turned out to be less toxic than curcumin. As evidenced by capillary electrophoresis and transmission electron microscopy studies, 1 proved to inhibit the formation of large toxic Aβ oligomers, by shifting the equilibrium toward smaller nontoxic assemblies and to limit the formation of insoluble fibrils. These findings were supported by molecular docking and steered molecular dynamics simulations which confirmed the superior capacity of 1 to bind Aβ structures of different complexity. Remarkably, 1 also showed in vitro anti-inflammatory and antioxidant properties. In summary, the curcumin-based analogue 1 emerged as multipotent compound worthy to be further investigated and exploited in the Alzheimer's disease multitarget context.
Synthesis and biological evaluation of allylated and prenylated mono-carbonyl analogs of curcumin as anti-inflammatory agents
Liu, Zhiguo,Tang, Longguang,Zou, Peng,Zhang, Yali,Wang, Zhe,Fang, Qilu,Jiang, Lili,Chen, Gaozhi,Xu, Zheng,Zhang, Huajie,Liang, Guang
, p. 671 - 682 (2014/03/21)
Curcumin has been shown to possess anti-inflammatory activities but has been limited for its low stability and poor bioavailability. We have previously reported four series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MACs). In continuation of our ongoing research, we designed and synthesized 33 novel allylated or prenylated MACs here, and evaluated their anti-inflammatory effects in RAW 264.7 macrophages. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6, especially IL-6. The preliminary SAR and quantitative SAR analysis were conducted. Compound 14q is the most potent analog among them, and exhibits significant protection against LPS-induced death in septic mice. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.
