Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation and Pharmacokinetic modelling of Cyclooxygenase-2 (COX-2) inhibitor for the clinical treatment of Colorectal Cancer

ABSTRACT

Colorectal cancer is the third most frequent cause of cancer worldwide and is more prevalent in older individuals of all ages. The recent statistics from World Health Organisation (WHO) on cancer accounted for 1.93 million new cases of colorectal cancer alone, in 2020[1]. The exact cause of this disease is still unknown; however, obesity, sedentary lifestyle, and changed food consumption habit are thought to be driving forces. Earlier clinical studies have found non-steroidal anti-inflammatory drugs (NSAIDs) to be potent in treating colorectal cancer by inhibiting cyclooxygenase enzyme, and further research ascertained cyclooxygenase-2 gene (COX-2) inhibitors to be the most effective chemotherapy treatment. The aim of this study is to find the most effective inhibitor with a superior affinity against COX-2 protein and its pharmacological profile. The pre-established compound, parecoxib (PubChem ID: 119828) was taken up for Structure-based Virtual Screening to identify a novel compound (PubChem ID: 10151468) that has a strong binding affinity than the established compound. Additionally, the comparative studies of both the screened and established compounds were examined using the MD simulation approach to confirm structural stability. Our conclusion suggests that the virtual screened compound (PubChem ID: 10151468) could be a potential therapeutic for the treatment of colorectal cancer.

KEYWORDS:

• COX-2 inhibitors
• Colorectal cancer
• Molecular Docking
• Molecular Dynamics Simulation
• Virtual Screening

Acknowledgments

1. We thank Taif University Researchers Supporting Project Number (TURSP-2020/202), Taif University, Taif, Saudi Arabia

2. The authors are grateful to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs.

3. SKS thank Alagappa University, Department of Biotechnology (DBT), New Delhi (No. BT/PR8138/BID/7/458/2013, dated 23rd May, 2013), DST-PURSE 2nd Phase Programme Order No. SR/PURSE Phase 2/38 (G dated 21.02.2017 and FIST (SR/FST/LSI – 667/2016), MHRD RUSA 1.0 and RUSA 2.0 for providing the financial assistance. UP gratefully acknowledge Indian Council of Medical Research (ISRM/11/(19)/2017, dated: 09.08.2018).

4. SKS thankfully acknowledges the Tamil Nadu State Council for Higher Education (TANSCHE) for the research grant (Au/S.o. (P&D): TANSCHE Projects: 117/2021).

Disclosure statement

No potential conflict of interest was reported by the author(s).