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Rational Approaches, Design Strategies, Structure Activity Relationship and Mechanistic Insights for Esterase Inhibitors

[ Vol. 18 , Issue. 10 ]

Author(s):

Harbinder Singh, Jatinder Vir Singh, Navdeep Kaur, Mohit Sanduja, Gurpreet Singh, Preet Mohinder Singh Bedi and Sahil Sharma*   Pages 837 - 894 ( 58 )

Abstract:


Background: Esterase is an enzyme that splits esters into an acid and alcohol. Varieties of esterases are present in human body to control diverse set of cellular processes and execute their specific functions. It can be seen that any increase in metabolites produced by these enzymes lead to severe pathological conditions like Alzheimer disease, hypercholesterolemia etc.

Objective: Numerous esterase inhibitors have been developed and reported by the researchers around the globe, but not systematically summarized yet. Therefore, this assemblage focuses on various reported esterase inhibitors during recent past with detailed account of the design strategies employed for the synthesis of novel drug entities. The article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of inhibitors as esterase inhibition. The interactions with the amino acid residues responsible for esterase inhibitory potential of molecules have also been discussed. This compilation will be of great interest for the researchers working in the area of esterase inhibitors.

Conclusion: Rivastigmine derivatives (44-53), tacrine-piperazine hybrid (136), coumarin-benzofuran derivative (169), coumarin-benzylpiperidine hybrid (181) and phenylcinnamide derivative (220) found to be exerting cholinesterase inhibition with IC50 below the range of 1 nM. Whereas, flavone (258) has displayed anticholesterol esterase potential below 1 nM. Benzil like derivative, (273) has also been designed and reported to possess remarkable inhibitory potential (IC50 & lt; 1 nM) against carboxylesterase. These representative results place them in forefront as potential future drug candidates to further develop potent and specific esterase inhibitors.

Keywords:

Alzheimer disease, biological functions, butylcholinesterase, carboxylesterase, hypercholesterolemia, rivastigmine derivatives, tacrine-piperazine hybrid.

Affiliation:

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab, Department of Chemistry, Guru Nanak Dev University, Amritsar-143005 Punjab, School of Pharmaceutical Sciences, MVN University, Palwal-121105, Haryana, Rajendra Institute of Technology and Sciences, Sirsa-125055, Haryana, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab, Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab

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