Molecular Docking Studies of ROS Agent from Quinone Family to Reductase Enzymes:Implication in Finding Anticancer Drug Candidate
Hesti L.Wiraswati 1,2*
, Fida M. Warganegara3, Akhmaloka 3 and Muhamad A. Martoprawiro 41Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Sumedang 45363, Indonesia
2Department of Biomedical Sciences, Division of Parasitology, Faculty of Medicine, Universitas Padjadjaran, Universitas Padjadjaran, Sumedang 45363, Indonesia
3Department of Chemistry, Institut Teknologi Bandung, Bandung 40132, Indonesia
4Department of Computational Sciences, Institut Teknologi Bandung, Bandung 40132, Indonesia
Corresponding Author E-mail:hesti.lina@unpad.ac.id
Abstract:
Understanding the metabolism of cytotoxic compounds of quinone family is importance in cancer therapy because they have been successfully explored for their anti-tumor activity. Quinone which form radical semiquinone (by reductase enzymes) to generate Reactive Oxygen Species (ROS) is associated to be anticancer drug candidate. However, molecular mechanism of those compounds to reductase enzymes has not yet clearly understood.This study aimed to understand molecular interaction of quinones to oxidoreductase enzymes such as cytochrome P450 reductase or ubiquinone reductase (NQO1), or apoptosis inducing factor (AIF) which is recently reported as NADH:quinone reductase. In silico approach was applied to find the best affinity of each compound to enzymes. Optimize ligands were employed using Marvin sketch program. Molecular interaction using autodockvina software was built to measure important residues for quinone reduction. Docking analysis showed that generally quinones prefer bound to cytochrome P450 reductase rather than NQO1 or AIF. The number of ring seems affect to the affinity, but not for its functional groups. Residues analysis confirmed that reduction of quinone is NAD(P)H: dependent. The result revealedthat all ligands have high possibility to compete with their redox coupleswhich is needed in its capacity as an anti-cancer drug.
Keywords: Anticancer; Docking; Quinones; Reductase Enzymes; ROS Back to TOC