Secondary metabolites of Mirabilis jalapa structurally inhibit Lactate Dehydrogenase A in silico: a potential cancer treatment

International Conference on Advanced Materials for Better Future 2017

Kusumawati, R.^1 ; Nasrullah, A.H.^1 ; Pesik, R.N.^2 ; Muthmainah^3 ; Indarto, D.^1,4

Department of Physiology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia^1

Department of Pathological Anatomy, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia^2

Department of Anatomy, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia^3

Biomedical Laboratory, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia^4

关键词: Autodock vinas;    Energy metabolism;    Lactate dehydrogenase;    Lower energies;    Molecular docking;    Phytochemicals;    Protein data bank;    Secondary metabolites;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/333/1/012078/pdf
DOI  :  10.1088/1757-899X/333/1/012078

来源: IOP

【 摘 要 】

Altered energy metabolism from phosphorylated oxidation to aerobic glycolysis is one of the cancer hallmarks. Lactate dehydrogenase A (LDHA) is a major enzyme that catalyses pyruvate to lactate in such condition. The aim of this study was to explore LDHA inhibitors derived from Indonesian herbal plants. In this study, LDHA and oxamate molecular structures were obtained from protein data bank. As a standard ligand inhibitor, oxamate was molecularly re-validated using Autodock Vina 1.1.2 software and showed binding energy -4.26 ± 0.006 kcal/mol and interacted with LDHA at Gln99, Arg105, Asn137, Arg168, His192, and Thr247 residues. Molecular docking was used to visualize interaction between Indonesian phytochemicals and LDHA. Indonesian phytochemicals with the lowest binding energy and similar residues with standard ligand was Miraxanthin-III (-8.53 ± 0.006 kcal/mol), Vulgaxanthin-I (-8.46 ± 0.006 kcal/mol), Miraxanthin-II (-7.9 ± 0.2 kcal/mol) and Miraxanthin-V (-7.96 ± kcal/mol). Lower energy binding to LDHA and binding site at these residues was predicted to inhibit LDHA activity better than standard ligand. All phytochemicals were found in Mirabilis jalapa plant. Secondary metabolites in Mirabilis jalapa have LDHA inhibitor property in silico. Further in vitro study should be performed to confirm this result.