Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, β-glucuronidase inhibition activity, crystal structure, and POM analyses

Abstract

A series of 15 novel compounds incorporating the thieno[2,3-b]thiophene moiety were synthesized. The chemical structures of these compounds were deduced from elemental analyses, 1 H NMR, 13 C NMR, and ESI-mass spectral data. The enzyme inhibition potential of these compounds was evaluated, in vitro, against β-glucuronidase, xanthine oxidase, and α-chymotrypsin enzymes. The cytotoxicity was evaluated by a cell viability assay utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Among the compounds tested, compound 3 was the most potent β-glucuronidase inhibitor with an IC 50 value of 0.9 ± 0.0138 μM; it was much more active than the standard, d-saccharic acid 1,4-lactone (IC 50 = 45.75 ± 2.16 μM). Compound 12, on the other hand, was the most potent as a xanthine oxidase inhibitor with an IC 50 of 14.4 ± 1.2 μM. With the characterization of their mechanism of action and with further testing, these compounds could be useful candidates as anticancer drugs. In addition, the newly synthesized compounds were subjected to POM analyses to get insights about their degree of their toxicity.