IN SILICO STUDY OF ANTICANCER ACTIVITY OF PYRAZOLINE C AND M AS POTENTIAL SELECTIVE OF CYCLOOXYGENASE-2 (COX-2) INHIBITOR USING MOLECULAR DOCKING AND MD SIMULATIONS

DENNY SATRIA; SYUKUR BERKAT WARUWU; ETI NURWENING SHOLIKHAH; MUSTOFA; PAMUNGKAS  BAGUS SATRIYO; TUTIK DWI WAHYUNINGSIH; HESTI I. WIRASWATI; EMA  DAMAYANTI

doi:10.22159/ijap.2024v16s4.52247

Authors

DENNY SATRIA Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan-20155, Indonesia https://orcid.org/0000-0003-4724-3256
SYUKUR BERKAT WARUWU Faculty of Pharmacy and Health Sciences, Universitas Sari Mutiara Indonesia, Medan-20123, Indonesia
ETI NURWENING SHOLIKHAH Department of Pharmacology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta-55281, Indonesia
MUSTOFA Department of Pharmacology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta-55281, Indonesia
PAMUNGKAS BAGUS SATRIYO Department of Pharmacology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta-55281, Indonesia
TUTIK DWI WAHYUNINGSIH Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta-55281, Indonesia
HESTI I. WIRASWATI Parasitology Division, Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung-45363, Indonesia
EMA DAMAYANTI Research Center for Food Technology and Processing, National Research and Innovation, Agency, Gunungkidul-55861, Indonesia

DOI:

https://doi.org/10.22159/ijap.2024v16s4.52247

Keywords:

Pyrazolines C and M, COX-2, Anticancer drugs, Molecular docking, MD simulation

Abstract

Objective: This study has been carried out with an in silico approach to predict interactions between drug candidates and receptor COX-2 (5IKT) and analysed the Molecular Dynamic (MD) simulation.

Methods: The docking procedure was executed with the MolDock algorithm, which was incorporated into Molegro Virtual Docker 5.0, employing the specific docking strategy. MD simulation was analysed with GROMACS 2019 for a duration of 50 nanoseconds. A graph is used to illustrate the interpretation of MD, depicting the Root mean Square Deviation (RMSD) on the backbone, the RMSF on C-alpha, and the Solvent-Accessible Surface Area (SASA) on the protein. This is accomplished via the qtGrace program.

Results: Pyrazoline C and M were used as ligands and celecoxib as a commercial drug. Pyrazoline M was the ligand with the highest affinity (-103.463 Kcal/mol) if compared with Pyrazoline C (-100.900 Kcal/mol), native ligand tolfenamic acid (-87.588 Kcal/mol) and celecoxib (-95.832 Kcal/mol). The molecular dynamics simulation for 50 ns was showed that RMSD, RMSF and SASA rigid and stable.

Conclusion: Pyrazoline C and M was the potential to develop as a breast cancer drug with COX-2 inhibitory activity.

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