Introduction: The signalling function of 2-arachidonoylglycerol (2-AG) in endocannabinoid
system is delineated by Monoacylglycerol lipase (MAGL). MAGL readdresses the lipid stores in the
direction of pro-tumorigenic signalling lipids in cancer cells. Selective as well as potent MAGL inhibitors
are limited in number hence their continuous development may lead to a breakthrough invention in
the field of MAGL inhibitors. In succession of the above, we have synthesised 2-amino-4-
methylthiazole-5-carboxylate derivatives and characterised them by collective use of IR, 1H-NMR,
13C-NMR, Mass spectral data and elemental analysis.
Methodology: Thirteen compounds (3c-g, 4c, 4e, 4f and 6b-f) inhibited MAGL with IC50 value 0.037-
9.60 μM. Two compounds (3g and 4c) were found to be most potent with IC50 values 0.037 and
0.063μM, respectively. Thirty synthesised compounds were sent to NCI for anticancer screening, out
of which nine compounds were selected for one dose anticancer assay. Compounds 3g (NSC:788170)
and 4c (NSC:788176)were found to be the most potent during one dose anticancer screening and fulfilled
the specified threshold for growth inhibition criteria of NCI and were further selected for full
panel five dose assay at 10-fold dilutions of five different concentrations.
Conclusion: Compound 3g displayed GI50 value 0.865 μM against EKVX (Non-Small Cell Lung Cancer
cell line), and 1.20 μM against MDA-MB-468 (Breast Cancer cell Line), while (4c) showed GI50
value 0.34 and 0.96 μM against HOP-92 and EKVX (Non-Small Cell Lung Cancer cell line) and 1.08
μM against MDA-MB-231/ATCC(Breast Cancer cell Line). In addition, molecular docking studies of
the said MAGL inhibitors have also been presented in this article.