Design, synthesis and biological evaluation of monoglyceride lipase inhibitors guided by dipeptidyl peptidase IV inhibitors

Kintscher U, Foryst-Ludwig A, Haemmerle G, Zechner R. The role of adipose triglyceride lipase and cytosolic lipolysis in cardiac function and heart failure. Cell Rep Med. 2020;1:100001–13. https://doi.org/10.1016/j.xcrm.2020.100001

Article  PubMed  PubMed Central  CAS  Google Scholar 

Taschler U, Radner FP, Heier C, Schreiber R, Schweiger M, Schoiswohl G, et al. Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem. 2011;286:17467–77. https://doi.org/10.1074/jbc.M110.215434

Article  PubMed  PubMed Central  CAS  Google Scholar 

Deng H, Li W. Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders. Acta Pharm Sin B. 2020;10:582–602. https://doi.org/10.1016/j.apsb.2019.10.006

Article  PubMed  CAS  Google Scholar 

Shahwan M, Alhumaydhi F, Ashraf GM, Hasan PM, Shamsi A. Role of polyphenols in combating Type 2 diabetes and insulin resistance. Int J Biol Macromol. 2022;206:567–79. https://doi.org/10.1016/j.ijbiomac.2022.03.004

Article  PubMed  CAS  Google Scholar 

Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, et al. Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019;26:25–32. https://doi.org/10.1177/2047487319878371

Article  PubMed  Google Scholar 

Wang Z, Yang B Polypharmacology in clinical applications: metabolic disease polypharmacology. Polypharmacology: principles and methodologies: Springer; 2022. p. 199-229.

Naser AY, Wong ICK, Whittlesea C, Beykloo MY, Man KK, Lau WC, et al. Use of multiple antidiabetic medications in patients with diabetes and its association with hypoglycaemic events: a case-crossover study in Jordan. BMJ open. 2018;8:e024909. https://doi.org/10.1136/bmjopen-2018-024909

Article  PubMed  PubMed Central  Google Scholar 

Ottanà R, Paoli P, Cappiello M, Nguyen TN, Adornato I, Del Corso A, et al. In search for Multi-Target ligands as potential agents for diabetes mellitus and its complications—a structure-activity relationship study on inhibitors of aldose reductase and protein tyrosine phosphatase 1B. Molecules. 2021;26:330. https://doi.org/10.3390/molecules26020330

Article  PubMed  PubMed Central  CAS  Google Scholar 

Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, et al. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci. 2010;13:1113–9. https://doi.org/10.1038/nn.2616

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sciolino NR, Zhou W, Hohmann AG. Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats. Pharmacol Res. 2011;64:226–34. https://doi.org/10.1016/j.phrs.2011.04.010

Article  PubMed  PubMed Central  CAS  Google Scholar 

Jaiswal S, Uniyal A, Tiwari V, Ayyannan SR. Synthesis and evaluation of dual fatty acid amide hydrolase-monoacylglycerol lipase inhibition and antinociceptive activities of 4-methylsulfonylaniline-derived semicarbazones. Bioorg Med Chem. 2022;60:116698. https://doi.org/10.1016/j.bmc.2022.116698

Article  PubMed  CAS  Google Scholar 

Janssen FJ, van der Stelt M. Inhibitors of diacylglycerol lipases in neurodegenerative and metabolic disorders. Bioorg Med Chem Lett. 2016;26:3831–7. https://doi.org/10.1016/j.bmcl.2016.06.076

Article  PubMed  CAS  Google Scholar 

Cisar JS, Weber OD, Clapper JR, Blankman JL, Henry CL, Simon GM, et al. Identification of ABX-1431, a selective inhibitor of monoacylglycerol lipase and clinical candidate for treatment of neurological disorders. J Med Chem. 2018;61:9062–84. https://doi.org/10.1021/acs.jmedchem.8b00951

Article  PubMed  CAS  Google Scholar 

Nomura DK, Lombardi DP, Chang JW, Niessen S, Ward AM, Long JZ, et al. Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem Biol. 2011;18:846–56. https://doi.org/10.1016/j.chembiol.2011.05.009

Article  PubMed  PubMed Central  CAS  Google Scholar 

Alkabbani D, Dahabiyeh LA, Taha MO. Dipeptidyl peptidase-IV blockers potently inhibit monoglyceride lipase: investigation by docking studies and in vitro bioassay. Med Chem Res. 2023;32:165–75. https://doi.org/10.1007/s00044-022-02998-5

Article  CAS  Google Scholar 

Gil-Ordóñez A, Martín-Fontecha M, Ortega-Gutiérrez S, López-Rodríguez ML. Monoacylglycerol lipase (MAGL) as a promising therapeutic target. Biochem Pharmacol. 2018;157:18–32. https://doi.org/10.1016/j.bcp.2018.07.036

Article  PubMed  CAS  Google Scholar 

Ranjbar S, Mohammadabadi Kamarei M, Sakhteman A, Khoshneviszadeh M. Discovery of potential natural dipeptidyl peptidase-4 inhibitors for type-2 diabetes treatment via structure-based virtual screening. Trends Pharmacol Sci. 2019;5:137–44. https://doi.org/10.30476/tips.2019.83480.1026

Article  CAS  Google Scholar 

Makrilakis K. The role of DPP-4 inhibitors in the treatment algorithm of type 2 diabetes mellitus: when to select, what to expect. Int J Environ Res Public Health. 2019;16:2720–40. https://doi.org/10.3390/ijerph16152720

Article  PubMed  PubMed Central  CAS  Google Scholar 

Schalk‐Hihi C, Schubert C, Alexander R, Bayoumy S, Clemente JC, Deckman I, et al. Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution. Protein Sci. 2011;;20:670–83. https://doi.org/10.1002/pro.596

Article  PubMed  PubMed Central  CAS  Google Scholar 

National Center for Biotechnology Information. PubChem Patent Summary for WO-2024182223-A3, Synthesis and use of sulfonamide analogs of memantine and amantadine. Retrieved April 24, 2025 from https://pubchem.ncbi.nlm.nih.gov/patent/WO-2024182223-A3. 2025.

Klimochkin YN, Moiseev IK, Abramov OV, Vladyko GV, Korobchenko LV, Boreko EI. Synthesis and antiviral activity of sulfur-containing derivatives of adamantane. Pharm Chem J. 1991;25:489–92. https://doi.org/10.1007/BF00772006

Article  Google Scholar 

Klimochkin YN, Ivleva EA. Synthesis and Chemical Transformations of N-Adamantylated Amides. Russ J Org Chem. 2022;58:669–78. https://doi.org/10.1134/S1070428022050050

Article  CAS  Google Scholar 

Khusnutdinov RI, Shchadneva NA, Mayakova YY, Khisamova LF, Dzhemilev UM. Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes catalyzed by manganese compounds and complexes. Russ J Org Chem. 2011;47:1682–5. https://doi.org/10.1134/S1070428011110042

Article  CAS  Google Scholar 

Klimochkin YN, Shiryaev VA, Leonova MV. Antiviral properties of cage compounds. New prospects. Russ Chem Bull. 2015;64:1473–96. https://doi.org/10.1007/s11172-015-1035-y

Article  CAS  Google Scholar 

Laali KK, Kalkhambkar RG, Sutar SM. Recent advances in the synthesis of diverse libraries of small-molecule building blocks in ionic liquids (ILs). Synlett. 2022;33:617–36. https://doi.org/10.1055/s-0040-1719852

Article  CAS  Google Scholar 

Wase N, Tu B, Allen JW, Black PN, DiRusso CC. Identification and metabolite profiling of chemical activators of lipid accumulation in green algae. Plant Physiol. 2017;174:2146–65. https://doi.org/10.1104/pp.17.00433

Article  PubMed  PubMed Central  CAS  Google Scholar 

National Center for Biotechnology Information. PubChem Patent Summary for US-6635637-B2, Cyclic oxyguanidine protease inhibitors. Retrieved April 24, 2025 from https://pubchem.ncbi.nlm.nih.gov/patent/US-6635637-B2. 2025.

Spencer J, Patel H, Callear SK, Coles SJ, Deadman JJ. Synthesis and solid state study of pyridine- and pyrimidine-based fragment libraries. Tetrahedron Lett. 2011;52:5905–9. https://doi.org/10.1016/j.tetlet.2011.07.147

Article  CAS  Google Scholar 

Sarswat A, Kumar R, Kumar L, Lal N, Sharma S, Prabhakar YS, et al. Arylpiperazines for management of benign prostatic hyperplasia: design, synthesis, quantitative structure-activity relationships, and pharmacokinetic studies. J Med Chem. 2011;54:302–11. https://doi.org/10.1021/jm101163m

Article  PubMed  CAS  Google Scholar 

National Center for Biotechnology Information. PubChem Patent Summary for US-8338430-B2, N-substituted piperazines. Retrieved April 24, 2025 from https://pubchem.ncbi.nlm.nih.gov/patent/US-8338430-B2. 2025.

National Center for Biotechnology Information. PubChem Patent Summary fo

Comments (0)

No login
gif