Repurposing of a muscle relaxant drug thiocolchicoside as an anticancer agent

Abstract

Introduction: Conventional methods of drug discovery have somehow proved to be ineffective in terms of lengthy design, limited efficacy amongst multiple other reasons. Considering that “time” is an important factor in the process of drug discovery, it becomes necessary to look for newer methods. Drug repurposing can be considered as a suitable option in such scenarios; to treat cancer or diseases with rapid pathogenesis. Amongst the various types of cancer, breast cancer and more precisely triple-negative breast cancer (TNBC) has become a prevalent form. Objectives: To overcome the challenges of conventional methods, several bioinformatic tools may be used, particularly those involved in molecular docking (CASTp, Discovery Studio, AutoDock Tools, etc.). Materials and Methods: Thiocolchicoside is a semisynthetic drug that was traditionally used as an anti-inflammatory and analgesic. In this article, we repurpose thiocolchicoside to act mainly on the NF-kB pathway. RANK and RANKL are frequently detected in the oncogenic process and together they participate in cancer development through TRAF6 activating the NF-kB pathway. Molecular docking of thiocolchicoside against TRAF6-RANK can exhibit the potency of this drug against breast cancer. Results: It was observed that cell viability was decreased when different drug concentrations were used against TNBS cell lines in vitro as compared with the control sample. The cell viability observed was 100% in the control sample, 95.93% in 15.625 µM drug concentration, 62.33% in 31.25 µM, 55.56% in 62.5 µM, 53.66% in 125 µM, 44.17% in 250 µM, and 39.84% in 500 µM. Conclusion: Repurposing a drug with the help of molecular docking is an effective method of drug development that reduces the time and cost factor due to its already known safety. Molecular docking of thiocolchicoside against TRAF6-RANK exhibits its inhibitory effect, and it can be effectively used as an anticancer drug.