Structure-based modification of 3-/4-aminoacetophenones giving a profound change of activity on tyrosinase: From potent activators to highly efficient inhibitors

Inhibition of Mushroom Tyrosinase Activity by Orsellinates

“…22) You et al demonstrated that the introduction of a thiosemicarbazide group in aminoacetophenones transforms them from activators into inhibitors. 23) Among linear-chain orsellinates, inhibitory activity rose with increasing number of carbons in the alkyl chain-namely, n-butyl (90.59%)<n-pentyl (65.92%)<n-hexyl (58.55%)<n-octyl orsellinate (45.62%)-corroborating the findings of Huang et al, 13) who observed that the inhibitory properties of p-alkyl benzoic acids were potentiated by increasing the length of hydrocarbon chains. A similar result was obtained by Jiménez et al, 9) who found 4-hexylresorcinol to be more active than 4-ethylresorcinol in preventing L-3,4-dihydroxyphenylalanine (L-DOPA) oxidation to DOPA-quinone.…”

Design, Synthesis, Biological Evaluation and Inhibition Mechanism of 3-/4-Alkoxy Phenylethylidenethiosemicarbazides as New, Potent and Safe Tyrosinase Inhibitors

“…The inhibition of target compounds on the diphenolase activity of mushroom tyrosinase was investigated by the reported procedure [45][46][47][48][49][50][51][52][53] with some slight modifications. Briefly, all the synthesized compounds were screened for the diphenolase inhibitory activity of tyrosinase using L-DOPA as substrate.…”

“…The assay of inhibition mechanism and inhibition types of selected compounds 5a and 6a on mushroom tyrosinase was finished as the reported protocol. [45][46][47][48][49][50][51][52][53] Assay of Cytotoxicity of Selected Compounds 5a, 6e, 6g and 6t to 293T Cell Line The assay of cytotoxicity of selected compounds to the 293T cell line was finished as the generally reported protocol. [65][66][67][68][69][70] Briefly, the 293T cell suspension was prepared and 100 µL of the suspension was injected in each tube placed in 96-hole culture plate, and the culture plate was pre-cultured in the incubator for 24 h (37°C, 5% CO 2 ); 10 µL of different-concentration solution of 5a was added to each cell line tube and the final concentration of 5a was respectively kept in 31.25, 62.5, 125, 250, 500, 1000 µmol/L; The culture plate was incubated for 24 h in the incubator, then 10 µL of CCK-8 solution was added into each tube in 96-hole plate; After the culture plate was incubated for 4 h in the incubator, the absorbance of the mixture in each tube at 450 nm was determined using micro-plate reader.…”

“…Although the crystallographic structure of tyrosinase revealed that there is a lipophilic long-narrow gorge near to the binuclear copper active center, [57][58][59] which may be related the enzyme inhibitory mechanism, and the specific mode of the interaction between the thiosemicarbazone molecule with these two copper ions in the active center of tyrosinase has been reported, 45) the detailed binding process of inhibitors to these two copper ions is still not known. According to the information provided in-house [51][52][53] (Fig. 1) and from other groups, 42,[54][55][56] thirty-nine novel 3-/4-alkoxy substituted phenylethylidenethiosemicarbazide derivatives bearing both a thiosemicarbazone moiety and a proper alkoxy lipophilic group were designed and synthesized, and their inhibitory effects on mushroom tyrosinase were evaluated.…”

Microwave‐assisted synthesis and biological evaluation of new thiazolylhydrazone derivatives as tyrosinase inhibitors and antioxidants

“…Klabunde et al reported that phenyl thioureas, thiazole ring, and alkyl thioureas exhibited weak to moderate inhibition of tyrosinase activity . Similarly, thiosemicarbazide derivatives and curcumin showed potential ability to coordinate the two copper ions in the active site of tyrosinase . Lately, our group described that thiosemicarbazide derivatives exhibited potent inhibitory activities against mushroom tyrosinase and the lead compounds could potentially bind to the binuclear active site of tyrosinase to inhibit its activity .…”