Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones

New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 +/- 0.11 to 44.80 +/- 2.34 mu M, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 +/- 032 to 192.10 +/- 3.78 mu M. The most active derivative exhibits a potent inhibition on IAP with a similar to 14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes.