International Journal of Drug Delivery Technology
Volume 15, Issue 2

Molecular Docking, MD Simulation, and Antiproliferative Activity of Pyridazine Derivatives

Ritik Panwar1, Vikash Jakhmola1*, Supriyo Saha1, Sunil Jawla2, Ravinesh Mishra3

1Department of Pharmaceutical Chemistry, Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun-248001, Uttarakhand, India

2Geeta Institute of Pharmacy, Geeta University, Panipat, Haryana, India

3School of Pharmacy and Emerging Sciences, Baddi University of Emerging Sciences & Technology, Baddi, Himachal Pradesh, India 

Received: 4th Mar, 2025; Revised: 11th Apr, 2025; Accepted: 7th Jun, 2025; Available Online: 25th Jun, 2025

ABSTRACT

Pyridazine derivative showed much diversified activity. Previously 77 pyridazine derivatives were synthesized and evaluated the antihypertensive property.  Pyridazine derivatives also showed antitumor and antiproliferative behavior. By kept this idea in mind we repurposed those pyridazine derivatives towards antiproliferation using in silico, and in vitro methods. Molecular docking analysis of pyridazine derivatives against DNA (PDB id: 6BNA) were performed and top4 molecules (R45, R60, R67, R70) were identified based on their docking scores. Then 100 ns MD simulation and MMPBSA analysis of these molecules were performed using GROMACS software. MD simulation data showed good RMSD, radius of gyration, SASA, and hydrogen bond analysis. Pyridazine derivative (R67) showed good simulation behavior with very minimum fluctuation within the receptor. Free binding energy of R67 was (-) 42.683 kJ/mol. R67 showed marked GI50 value against MCF7 cell line using sulphorhodamine assay. Among the pyridazine derivatives Among the synthesized molecules 6-([1,1'-biphenyl]-4-yl)-2-(4-([1,1'-biphenyl]-4-yl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one (R67) showed best antiproliferative activity with in silico insights.

Keywords: Pyridazine, Molecular docking, MD Simulation, Antiproliferative.

How to cite this article: Ritik Panwar, Vikash Jakhmola, Supriyo Saha, Sunil Jawla, Ravinesh Mishra. Molecular Docking, MD Simulation, and Antiproliferative Activity of Pyridazine Derivatives. International Journal of Drug Delivery Technology. 2025;15(2):748-56. doi: 10.25258/ijddt.15.2.48

Sourse of support: This study is supported by Division of Research & Innovation, Uttaranchal University, Dehradun, India under the seed money grant reference no UU/DRI/SM/2024-25/018.

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