Molecular Interaction and Inhibitory Potential of Polyphenol on DNA Repair Pathway in Small Cell Lung Cancer: A Computational Study

Abstract

Poly ADP ribose polymerase parp is a ubiquitous and transient nucleo protein with supra function in orchestrating DNA damage repair symphony and has prognostic value in small cell lung cancer SCLC Accumulating evidence indicate that the substrate NAD binding catalytic domain active site of this protein launches its activation However blocking this binding site is the key node in the inhibition of DNA repair pathway thus signifying its importance in the control of small cell lung cancer progression Approved drugs for the treatment of disease burden may stop the growth of the tumor cells by blocking some of the enzymes needed for cell growth or by killing the cells stopping them from dividing via combinatorial efficacy Clinical tractability of this strategy has been proven to potentially promote undesirable side effect In the current study our aim therefore was to outsource a best in class small molecule inhibitor of PARP from health friendly source We therefore employed computational tools to investigate the therapeutic relevance of compounds from natural source as parp inhibitor via molecular docking approach phyto compounds were retrieved from the selected plant gallocatechin GC a polyphenolic compound showed best binding affinity with the catalytic domain active site of parp on comparism to the standard inhibitors GC interact with the amino acid residue around the of the catalytic domain ASN ASN SER GLY HIS TYR PHE TRP ALA SER TYR LYS as evaluated by energy decomposition per residue of GC parp complex The result from this investigation thus project GC as a lead compound which may inhibit PARP as a single therapy in the treatment of small cell lung cancer