Bio-evaluation of the p-(arylsulfonyl)benzaldehydes against tyrosinase, lipoxygenase-15 (LOX-15) and inducible nitric oxide synthase (iNOS)

• The p -(arylsulfonyl)benzaldehydes 3a – f strongly inhibited tyrosinase compared to kojic acid • Some of the derivatives also inhibited the activity of LOX-15 and/or iNOS • The test compounds exhibited reduc ed cytotoxicity against the Hek293-T compared to doxorubicin • Hydrogen bonding and hydrophobic interactions stabilize receptor-ligand complexes A series of the p -(arylsulfonyl)benzaldehydes was synthesized to study their enzyme inhibitory properties targeting tyrosinase, lipoxygenase-15 (LOX-15) and inducible nitric oxide synthase (iNOS). All of these biochemical targets are implicated in the onset and/or progression of chronic inflammation-linked diseases and oxidative stress such as hyperpigmentary disorders in human skin, cancer, diabetes and neurodegenerative disorders. Except for the 4-(trifluoromethylphenyl)sulfonyl derivative 3g (IC 50 = 26.38 ± 0.03 µM) all of the other test compounds exhibited superior inhibitory effect against tyrosinase compared to kojic acid (IC 50 = 24.25 ± 0.14 µM) with the IC 50 values in the range 3.82 ± 0.03 – 19.38 ± 0.05 µM. Compounds 3a – f exhibited dual inhibitory effect against tyrosinase and either LOX-15 or iNOS. The test compounds exhibited reduced cytotoxicity against the human embryo kidney derived Hek293-T cell compared to the clinical drug, doxorubicin, at the concentrations tested. The formylphenyl and arylsulfonyl rings are predicted to engage in hydrophobic and π-π stacking and/or T-shaped interactions with hydrophobic pockets of the test enzymes.