Implication of Integrated in Silico Docking and Moma Simulation for the Development of Curcuminoids as Sphingosine Kinase 1 (SK1) Inhibitors for Cancer Treatment Volume 3 - Issue 3

Noboru Motohashi¹, Anuradha Vanam², Jyothirmayi Vadapalli³ and Rao Gollapudi⁴*

• ¹Meiji Pharmaceutical University, Japan
• ²Sri Venkateswara University, India
• ³Acharya Nagarjuna University, India
• ⁴University of Kansas, USA

Received:January 02, 2020   Published: January 23, 2020

Corresponding author: Rao Gollapudi, University of Kansas, USA

DOI: 10.32474/OAJOM.2020.03.000165

 

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Abstract

Sphingosine kinase 1 (SphK1) enzyme catalyzes the phosphorylation of sphingosine into sphingosine-1-phosphate (S1P). S1P plays an important role in diverse biological processes. In numerous human cancers, overexpression of SphK1 led to the severity of disease, drug resistance and reduced patient survival. Furthermore, SphK1 increased activity was connected to play a crucial role in immunological responses such as asthma, rheumatoid arthritis and sepsis. Inhibitors of SphK1 enzyme helps in reducing the adverse effects caused by over expression of SpkH1. Hence, there is a growing demand for the discovery of new SphK1 inhibitors. Curcumin (5) a major constituent of turmeric rhizomes, displayed the inhibition activity of cancers by regulating multiple cellular signaling pathways. Henceforth, the present molecular docking study suggested that curcumin (5) could be valuable SphK1 inhibitor as a result of its binding affinity to the SphK1 active site similar to that of CTK8F1052 (4). Further exploration of curcumin (5) efficacy in inhibiting the SphK1 activity is necessary to support computational docking findings.

Keywords: Sphingosine Kinase1; Sphingosine-1-Phosphate; Adenosine Triphosphate; CTK8F1052; Curcumin; Cyclophosphamide; Docetaxel; Doxorubicin; Cellular Pathways; Cancer; Lipinski’s Rule of Five; In Silico Docking Studies.

List of Abbreviations: SIP: Sphingosine-1-Phosphate; GTP-G: Guanosine Triphosphate; G-Protein: Binding Protein; GRK: Coupled Receptor Kinases; S1P: Sphingosine-1-Phosphate; SphK: Sphingosine Kinase; ATP: Adenosine Triphosphate; TNBC: Triple Negative Breast Cancer; CVDs: Cardiovascular Disorders; SK: Sphingosine Kinase; ER: Estrogen Receptor; PDB: Protein Data Bank; MVD: Molegro Virtual Docking; MMFF: Merck Molecular Force Field

Abstract| Introduction| Materials and Methods| Results and Discussion| Conclusion| References|