Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents
Wabdan, A., Mahdi, M., Khan, A. (2021). Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents. EKB Journal Management System, 64(8), 4311-4322. doi: 10.21608/ejchem.2021.64042.3377
Ammar Kadhim Wabdan; Monther Faisal Mahdi; Ayad Kareem Khan. "Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents". EKB Journal Management System, 64, 8, 2021, 4311-4322. doi: 10.21608/ejchem.2021.64042.3377
Wabdan, A., Mahdi, M., Khan, A. (2021). 'Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents', EKB Journal Management System, 64(8), pp. 4311-4322. doi: 10.21608/ejchem.2021.64042.3377
Wabdan, A., Mahdi, M., Khan, A. Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents. EKB Journal Management System, 2021; 64(8): 4311-4322. doi: 10.21608/ejchem.2021.64042.3377

Molecular Docking, Synthesis and ADME Studies of New Pyrazoline Derivatives as Potential Anticancer Agents

Egyptian Journal of Chemistry
Article 34, Volume 64, Issue 8, August 2021, Page 4311-4322  XML PDF (1.41 MB)
Document Type: Original Article
DOI: 10.21608/ejchem.2021.64042.3377
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Authors
Ammar Kadhim Wabdan1; Monther Faisal Mahdiorcid 2; Ayad Kareem Khan email orcid 3
1Department of pharmaceutical chemistry/ college of pharmacy/ Mustansiriya University/ Baghdad/ Iraq
2pharmaceutical chemistry department, college of pharmacy, Mustansiriyah University, Baghdad- Iraq
3Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad - Iraq.
Abstract
ABSTRACT
Cancer is a significant worldwide public health issue.The adverse effects of anticancer chemotherapies still compromise the quality of life of patients .To identify new potential targeted anticancer agents, a series of pyrazoline derivatives were synthesized and evaluated for anticancer effects on A549 (human lung adenocarcenoma cell line). The new derivatives were synthesized by incorporating pyrazoline pharmacophore into nabumetone moiety as a starting molecule and the chalcone derivatives as intermediate products. In silico evaluation methods were done before synthesis through .molecular docking via genetic optimization for ligand docking (GOLD) Suite software with EGFR tyrosine kinase and exhibited significant tyrosine kinase inhibition activities compared with erlotinb as a reference drug due to their hydrogen bonding interaction with key amino acids and these results are compatible with the experimental findings . The Compound structures were confirmed by 1H-NMR , some physicochemical properties and infrared spectroscopy . An in vitro assay demonstrated that the final compounds (P1,P2,P3 and P4) exerted potent to moderate cytotoxic activity in the micromolar range with an IC50 values (15.409µM, 7.24µM, 27.05µM, 22.45µM) respectively when compared with erlotinib (IC50 =25.23µM) while (P5&P6) show weak activity . Pharmacokinetic and physicochemical properties of the final compounds predicted by using ADME Evaluations . The results showed all the synthesized compounds have high oral bioavailability and good GI absorption.
Keywords
Synthesis; Anticancer; Nabumetone; Pyrazoline; Docking studies
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