Computational modeling of hepatocellular carcinoma associated PARP-1 protein and structure base screening of potential inhibitor
Santosh Kumar Jha
Birla Institute of Technology, Ranchi, India
: J Pharm Drug Deliv Res
Abstract
Hepatocellular carcinoma is one of the hard-treating and high mortality cancers for which novel therapies are very much in need. There are many complications and side-effects in present available treatment modalities, there is only one drug that is in use (Sorafenib) and many are under clinical trials. So, some proteins were found which were responsible for causing Hepatocellular carcinoma. One of these proteins was selected and targeted, and its inhibitors were found, which inhibit the activity of that protein to cause HCC. Here, in silico approach was directed to find the novel inhibitor as potential candidate therapy for HCC. Here, Poly[ADP-ribose]polymerase-1 (PARP-1) was used as druggable target. Total 20 inhibitors of PARP-1 in 91 conformations were used for standard precision computational docking. On the basis of docking score and glide score, suitable inhibitors were identified. These selected inhibitors can be used as lead molecules for the designing of inhibitor based drugs. Lead molecules were further characterised by ADMET analysis, which include Lipinski’s rule, Jorgensen’s rule, blood-brain barrier penetration, Skin permeability, Human intestinal absorption and oral absorption. C15H19N3O2+ was found to be best inhibitor of PARP-1 among all the inhibitors with best ADMET properties. So it may be a better alternative for the inhibition of PARP-1and preventing from HCC. Present study focuses on the importance of structure based in silico drug design which takes less time and is cost effective.
Biography
Email: skjha@bitmesra.ac.in
