Design, synthesis and comparison of water-soluble phthalocyanine/porphyrin analogues and their inhibition effects on Aβ42 fibrillization

The misfolding and fibrillization of beta amyloid (A beta) is a major pathological hallmark of Alzheimer's disease (AD) and creates an important niche for developing targeted probe and drug designs. Phthalocyanine and porphyrin analogues are known to interact with A beta species and interrupt their aggregation, and in this study we show that by conjugating with small molecules that can function as A beta aggregation blockers such as curcumin and bexarotene, drug candidates with improved potential can be developed. In this work, we investigated porphyrin zinc (ZnPorp) analogues and phthalocyanine zinc (ZnPc) conjugates and compared their inhibitory effects on the formation of A beta(42) fibrils. We show that probe designs with a good hydrophilic-hydrophobic balance as observed with the ZnPc conjugate analogues are deemed as better inhibitors in modulating A beta(42) aggregation.

Automated summary

Research shows that conjugating small molecules such as curcumin and bexarotene with phthalocyanine and porphyrins, which can function as Aβ aggregation blockers, can lead to the development of drug candidates with improved potential. Probe designs with a good hydrophilic-hydrophobic balance, like the ZnPc conjugate analogues, are considered better inhibitors in modulating Aβ(42) aggregation.