Synthesis and Pancreatic Lipase Inhibitory Activity of Phenacyl Esters of N-Aroyl Amino Acids

Author(s): Maida Engels Selvaraj Emimmal, Veintramuthu Sankar*.

Journal Name: Current Enzyme Inhibition

Volume 15 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Obesity has become a major life-threatening disorder as it is associated with many risk factors such as coronary heart disease, hypertension, type II diabetes and certain forms of cancer. Pancreatic lipase inhibition is one of the alternate strategies to treat obesity. In our previous study, phenacyl ester of N-sulphonyl beta alanine was obtained as a hit molecule when pharmacophore- based virtual screening was carried out using reported pancreatic lipase inhibitors.

Objective: In search of novel pancreatic lipase inhibitors, three series of phenacyl esters of Nsubstituted amino acids were synthesized and evaluated for their pancreatic lipase inhibitory activity.

Methods: N-aroylation of amino acids and subsequent esterification with different phenacyl bromides in the presence of N,N-Dimethylformamide (DMF) afforded the corresponding phenacyl esters in quantitative yields.

Results: The synthesized compounds were found to have good pancreatic lipase inhibitory activity and showed IC50 in the range of 0.036 and 84 μg/ml.

Conclusion: All the synthesized compounds showed better pancreatic lipase inhibitory activity and it indicates that the N-aroylated phenacyl esters could be considered as lead moiety for further studies to develop novel anti-obesity potentials.

Keywords: Amino acids, anti-obesity, N-aroyl amino acids, p-Nitrophenyl palmitate, pancreatic lipase, phenacyl ester.

[1]
Grundy, S.M. Obesity, metabolic syndrome, and cardiovascular disease. J. Clin. Endocrinol. Metab., 2004, 89(6), 2595-2600.
[http://dx.doi.org/10.1210/jc.2004-0372] [PMID: 15181029]
[2]
Hofbauer, K.G.; Nicholson, J.R.; Boss, O. The obesity epidemic: current and future pharmacological treatments. Annu. Rev. Pharmacol. Toxicol., 2007, 47, 565-592.
[http://dx.doi.org/10.1146/annurev.pharmtox.47.120505.105256] [PMID: 17002599]
[3]
Thomson, A.B.; De Pover, A.; Keelan, M.; Jarocka-Cyrta, E.; Clandinin, M.T. Inhibition of lipid absorption as an approach to the treatment of obesity. Methods Enzymol., 1997, 286, 3-44.
[http://dx.doi.org/10.1016/S0076-6879(97)86003-X] [PMID: 9309643]
[4]
Shi, Y.; Burn, P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat. Rev. Drug Discov., 2004, 3(8), 695-710.
[http://dx.doi.org/10.1038/nrd1469] [PMID: 15286736]
[5]
Maida Engels, S.E.; Balaji, B.; Divakar, S.; Geetha, G. Ligand based pharmacophore modelling, virtual screening and molecular docking studies to design novel pancreatic lipase inhibitors. Int. J. Pharm. Pharm. Sci., 2017, 9(4), 48-65.
[http://dx.doi.org/10.22159/ijpps.2017v9i4.16392]
[6]
Furniss, B.S.; Hannaford, A.J.; Rogers, V.; Smith, P.W.G.; Tatchell, A.R. Vogel Practical Organic Chemistry; Longman and ELBS, 2005.
[7]
Maurer, P.J.; Takahata, H.; Rapport, H. α-Amino Acids as chiral educts for asymmetric products. A general synthesis of D- α -amino Acids from L-serine. J. Am. Chem. Soc., 1984, 106(4), 1095-1098.
[http://dx.doi.org/10.1021/ja00316a047]
[8]
Deng, X.; Mani, N.S. A facile, environmentally benign sulfonamide synthesis in water. Green Chem., 2006, 8(9), 835-838.
[http://dx.doi.org/10.1039/b606127c]
[9]
Kazaryan, S.A.; Grigoryan, K.P.; Paronikyan, R.G.; Agaronyan, A.S.; Gevondyan, A.I.; Samvelyan, V.M. Synthesis and anticonvulsant activity of new N-benzoyl derivatives of aliphatic acids and their salts. Khim.-. Farm. Zh., 2001, 35(9), 21-23.
[10]
Caplar, V.; Lisini, A.; Kajfei, F.; Kolbah, D.; Sunjic, V. Synthesis of the 2,3-Dihydro-6H-1,4-oxazin-2-one Chiral at C(3) and asymmetric induction in hydrogenation of the azomethine bond. J. Org. Chem., 1978, 43(7), 1355-1360.
[http://dx.doi.org/10.1021/jo00401a015]
[11]
Winkler, U.K.; Stuckmann, M. Glycogen, hyaluronate, and some other polysaccharides greatly enhance the formation of exolipase by Serratia marcescens. J. Bacteriol., 1979, 138(3), 663-670.
[PMID: 222724]
[12]
Schmidt-Dannert, C.; Sztajer, H.; Stöcklein, W.; Menge, U.; Schmid, R.D. Screening, purification and properties of a thermophilic lipase from Bacillus thermocatenulatus. Biochim. Biophys. Acta, 1994, 1214(1), 43-53.
[http://dx.doi.org/10.1016/0005-2760(94)90008-6] [PMID: 8068728]


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 15
ISSUE: 2
Year: 2019
Page: [133 - 143]
Pages: 11
DOI: 10.2174/1573408015666190920092114

Article Metrics

PDF: 9