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Molecular docking of anti-inflammatory drug diclofenac with metabolic targets: Potential applications in cancer therapeutics
- Source :
- Journal of theoretical biology. 465
- Publication Year :
- 2018
-
Abstract
- Diclofenac is a potent NSAID of clinical choice, which is widely used for containing inflammation. Moreover, recent experimental evidences overwhelmingly substantiate its antineoplastic potential. However, the precise molecular mechanisms of diclofenac's anticancer activity remain poorly understood. Neoplastic cells display reprogrammed metabolic features, which are manifested and regulated by a complex networking of molecular pathways. However, the effect of diclofenac on tumor cell metabolism are not yet clearly deciphered. Hence, the present investigation was carried out to identify and characterize key diclofenac targets of tumor metabolism, cell survival and chemoresistance. The interactions of diclofenac with such targets was analysed by PatchDock and YASARA (Yet Another Scientific Artificial Reality Application). The docking ability of diclofenac with its targets was based on analysis of dissociation constant (Kd), geometric shape complementarity score (GSC score), approximate interface area (AI area) and binding energy. The findings of this investigation reveal that diclofenac is capable of interacting with all of the selected molecular targets. Prominent interactions were observed with GLUT1, MCT4, LDH A, COX1, COX2, BCRP/ABCG2, HDM2/MDM2 and MRP1 compared to other targets. Interactions were of noncovalent nature involving ionic, hydrophobic interactions, Van der Waals forces and H-bonds, which varied depending on targets. This study for the first time, characterizes the nature of molecular interactions of diclofenac with selected targets involved in cancer cell metabolism, pH homeostasis, chemosensitivity, cell signalling and inflammation. Hence, these findings will be highly beneficial in optimizing the utility of diclofenac in development of novel cancer therapeutics.
- Subjects :
- 0301 basic medicine
Statistics and Probability
Drug
Monocarboxylic Acid Transporters
Cell signaling
Diclofenac
Abcg2
Protein Conformation
media_common.quotation_subject
Muscle Proteins
Inflammation
Pharmacology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Neoplasms
medicine
ATP Binding Cassette Transporter, Subfamily G, Member 2
Humans
media_common
Glucose Transporter Type 1
General Immunology and Microbiology
biology
Molecular Structure
Chemistry
Applied Mathematics
Anti-Inflammatory Agents, Non-Steroidal
Proto-Oncogene Proteins c-mdm2
General Medicine
Neoplasm Proteins
Molecular Docking Simulation
stomatognathic diseases
Kinetics
030104 developmental biology
Docking (molecular)
Modeling and Simulation
Cancer cell
biology.protein
Cyclooxygenase 1
Mdm2
medicine.symptom
General Agricultural and Biological Sciences
030217 neurology & neurosurgery
medicine.drug
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 10958541
- Volume :
- 465
- Database :
- OpenAIRE
- Journal :
- Journal of theoretical biology
- Accession number :
- edsair.doi.dedup.....5c40c349cbbc1574eac3c94fd2a306c9