Synthesis, Structure-Activity Relationships and Biological Activity of New Isatin Derivatives as Tyrosinase Inhibitors
Nahit Gencer, Fatih Sonmez, Dudu Demir, Oktay Arslan and Mustafa Kucukislamoglu
Affiliation: Department of Chemistry, Faculty of Art and Sciences, Balikesir University, Balikesir, 10145, Turkey.
A newly series of isatin derivatives (6a-t) containing alkyl/aryl urea groups were synthesized and their inhibitory
effects on the diphenolase activity of banana tyrosinase were evaluated. Tyrosinase was purified from banana on an
affinity gel comprised of Sepharose 4B-L-tyrosine-p-aminobenzoic acid. The results showed that all the synthesized compounds
inhibited the tyrosinase enzyme activity. Among them, 1-(2,3-dioxoindolin-5-yl)-3-(4-nitrophenyl)urea (6l) was
found to be most active compound (Ki = 24.96 µM). The inhibition kinetics was analysed by Lineweaver-Burk double reciprocal
plots. It revealed that compound 6l was a competitive inhibitor. According to results of structure-activity relationship,
generally, the compounds electron-donating group bonded to the phenyl ring have higher inhibitory activity against
tyrosinase than halogen group bonded to the phenyl ring. The inhibitory activities of alkyl urea substituted compounds decreased
with increasing carbon number of the alkyl groups at urea moiety. The halogen series at the para position of the
phenyl ring showed a qualitative relationship for higher inhibitory activity with increasing size and polarizability. HOMOLUMO
energy levels and dipole moments of some selected compounds (6a, 6d, 6h, 6l and 6o) were also calculated by
Keywords: Inhibition, isatin, structure-activity relationships, synthesis, tyrosinase, urea.
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