Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study

• DOI: 10.1007/s10822-016-9932-1
• Publication Date: 2016-08-10T11:48:34Z
• Authors: Nguyen Quoc Thai; Ning-Hsuan Tseng; Mui Thi Vu; Tin Trung Nguyen; Huynh Quang Linh; Chin-Kun Hu; Yun-Ru Chen; Mai Suan Li
• Keywords: Amyloid beta; Amyloid (mycology)

Combining Lipinski's rule with the docking and steered molecular dynamics simulations using PubChem data base of about 1.4 million compounds, we have obtained DNA dyes Hoechst 34580 33342 as top-leads for Alzheimer's disease. The binding properties these ligands to amyloid beta (Aβ) fibril were thoroughly studied by in silico vitro experiments. prefer locate near hydrophobic regions affinity mainly governed van der Waals interaction. By Thioflavin T assay, it was found that inhibition constant IC50 ≈ 0.86 0.68 μM 33342, respectively. This result qualitatively agrees free energy estimated mechanic-Poisson Boltzmann surface area method all-atom AMBER-f99SB-ILDN force field water model TIP3P. In addition, high capability cross blood brain barrier. Thus, both experiments shown are good candidates treating disease inhibiting Aβ formation.