Synthesis of new class of indole acetic acid sulfonate derivatives as ectonucleotidases inhibitors

Abstract

-TNAP = 0.59 ± 0.08 μM, 36 folds increase with respect to Levamisole). Molecular docking studies revealed that inhibitors of these selected target enzymes induced favorable interactions with the key amino acids of the active site, including Lys255, Lys278, Asn277, Gly533, Lys528, Tyr451, Phe257, Tyr340, Gln465, Gln434, Lys437, Glu830, Cys818, Asn499, Arg40, Phe417, Phe500, Asn503, Asn599, Tyr281, Arg397, Asp526, Phe419 and Tyr502. Enzyme kinetic studies revealed that potent compounds such as 5j and 5e blocked these ectonucleotidases competitively while compounds 5e and 5c presented an un-competitive binding mode. 5g revealed a non-competitive mode of inhibition.

Topics & Concepts