1246384-08-6Relevant articles and documents
Synthesis, computational molecular docking analysis and effectiveness on tyrosinase inhibition of kojic acid derivatives
Karakaya, Gül?ah,Türe, Asl?,Ercan, Ay?e,?ncül, Selin,Aytemir, Mutlu Dilsiz
, (2019)
Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4H-pyran-4-one structure (compounds 1–30)with inhibitory effects on tyrosinase enzyme were described. One-pot Mannich reaction was carried out by using kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in presence of formaline. Subsequently, cyclic amine (morpholine, piperidine and pyrrolidine)derivatives of the 6th-position of chlorokojic acid were obtained with nucleophilic substitutions in basic medium. The structures of new compounds were identified by FT-IR, 1H- and 13C NMR, ESI-MS and elemental analysis data. The potential mushroom tyrosinase inhibitory activity of the compounds were evaluated by the spectrophotometric method using L-DOPA as a substrate and kojic acid as the control agent. The potential inhibitory activity was also investigated in silico using molecular docking simulation method. Tyrosinase inhibitory action was significantly more efficacious for several compounds (IC50: 86.2–362.1 μM)than kojic acid (IC50: 418.2). Compound 3 bearing 3,4-dichlorobenzyl piperazine moiety was proven to have the highest inhibitory activity. The results of docking studies showed that according to the predicted conformation of compound 3 in the enzyme binding site, hydroxymethyl group provides a metal complex with copper ions and enzyme. Thus, this interaction explain the high inhibitory activities of the compounds 1, 3 and 4 possessing hydroxymethyl substituent supporting the mushroom assay results with docking studies. In accordance with the results, it is suggested that Mannich bases of kojic acid bearing substituted benzyl piperazine groups (compounds 1, 3, 4, 11, 13, 14, 23, 24, 28, and 29)could be promising antityrosinase agents. Additionally, considering the relationship between tyrosinase inhibitory activity results and molecular docking, a new tyrosinase inhibition mechanism can be proposed.
A study of cytotoxicity of novel chlorokojic acid derivatives with their antimicrobial and antiviral activities
Aytemir, Mutlu Dilsiz,?zelik, Berrin
experimental part, p. 4089 - 4095 (2010/10/02)
A series of 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives were synthesized and tested for their antimicrobial and antiviral activities. Mannich base derivatives were prepared through the reaction of substituted piperazine or piperidine derivatives on chlorokojic acid and formaline. The structures of the synthesized compounds were confirmed by IR, 1H and 13C NMR, ESI-MS, and elemental analysis. According to the activity studies, compounds 2-7 (MIC: 1-2 μg/mL) were found to be highly active against Bacillus subtilis and Staphylococcus aureus, while compounds 3, 5 and 6 showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Also, compounds 2-7 were more remarkably active against Candida albicans and Candida parapsilosis (MIC: 4-8 μg/mL). Additionally, compound 2 was the most active one against RNA virus PI-3. Seven novel 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one derivatives (compounds 1-7) were synthesized and tested for their antimicrobial and antiviral activities.
