Jahangir Alam, Varun Jaiswal* and Lalit Sharma Pages 1 - 8 ( 8 )
Background: β-amyloid (Aβ) production and aggregation is the main culprit of Alzheimer’s disease (AD). AD is becoming crisis where no treatment available for halting the disease progression. Antibiotics are used not only to treat infections, but also some of the non-contagious diseases and have found active as anti-amyloidogenic agents.
Objective: The work aim’s to investigate anti-amyloidogenic activity of antibiotics as re-purposing agents via inhibiting Aβ aggregation and fibril formation employing in-silico and in-vitro approaches.
Mehtods: In-silico screening was designed with receptor and ligand preparation, grid formation, docking simulation and its analysis. Thioflavin T-amyloid binding and protease-digestion studies were intended as in-vitro assays. The pharmacological potential of antibiotics as anti-amyloidogenic agents was assessed by these methods.
Results: Paromomycin and Neomycin were identified with higher order of estimated free energy of binding in in-silico sreening. In in-vitro screening, paromomycin significantly (p<0.01) reduced the fluorescence intensity and resistance to tryptic degradation of Aβ(1-42) peptides while neomycin had no or little effect (p<0.01) when compared to control. Results from docking and wet lab studies were found in correlation.
Conclusion: Paromomycin exhibited higher anti-Aβ aggregating and defibrillogenic activity than neomycin and leaves an indication for further in-vivo testing and could be a future promising anti-amyloidal candidate for the treatment of several amyloidoses.
Alzheimer’s Disease, β-amyloid (Aβ) aggregation, Aβ fibril, Antibiotics, Molecular docking, Drug re-purposing
School of Pharmaceutical Sciences, Shoolini University, Solan, H.P, School of Electrical and Computer Science Engineering, Shoolini University, Solan, H.P, School of Pharmaceutical Sciences, Shoolini University, Solan, H.P