Abstract

Microwave-assisted SiO2-H2SO4-catalyzed Synthesis of 3,4,6,7-Tetrahydro-3,3,6,6-Tetramethyl-9,10-diphenylacridine-1,8-dione Derivatives as Cholesterol Esterase Inhibitors

Author(s): H. Singh, H. Singh, A. Singh, M. K. Gupta1, S. Sharma* and P. M. S. Bedi
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, School of Pharmacy, Lloyd Institute of Management and Technology, Greater Noida-201308, India

Correspondence Address:
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, India, E-mail: [email protected]


A library of 3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-9,10-diphenylacridine-1,8-dione derivatives were synthesized via microwave-assisted three-component reaction employing silica supported sulphuric acid under solvent free conditions and tested for in vitro cholesterol esterase inhibitory activity. All synthesized compounds exhibited moderate to good inhibition of cholesterol esterase enzyme. Among all the synthesized acridinedione derivatives, compound HSM-1a showed the most promising activity with IC50 value of 1.53 µM against cholesterol esterase enzyme. Enzyme kinetic studies carried out for HSM-1a, revealed its mixed-type inhibition approach. Molecular protein–ligand docking studies were also performed to figure out the key binding interactions of HSM-1a with the amino acid residues of the enzyme’s active site. Furthermore, acquiescence of some potent compounds to the Lipinski rule was also determined.



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