Regioselective Enzymatic Synthesis of Kojic Acid Monoesters

Kojic acid is a fungal metabolite and one of the strongest tyrosinase inhibitors. Its esters are used as lipid-compatible skin whitening components in cosmetic formulations. In this study, lipase PS, lipase AK, Lipolyve AN and pig pancreatic lipase catalyzed the acetylation of kojic acid under selective formation of the same product, kojic 7-acetate. However, the enzymes differed in their regioselectivity when catalyzing the alcoholysis of kojic acid diacetate. While lipase PS and lipase AK produced mixtures of both monoacetate regioisomers (7-acetate and 5-acetate of kojic acid), the pancreatic lipase almost exclusively produced 5-acetate. The enzyme displayed the same regioselectivity in the palmitoylation of kojic acid and in the alcoholysis of kojic acid dipalmitate. Simple reaction engineering with PPL as a catalyst thus provides the complementary monoesters of kojic acid. Kojic 7-acetate, 5-acetate, 7-palmitate and 5-palmitate were prepared with yields after purification of 57.3%, 38.2%, 31.7% and 31.4%, respectively.

Download Full-text

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200627212128 ◽

2020 ◽

Vol 20 (14) ◽

pp. 1714-1721

Author(s):

Hatem A. Abuelizz ◽

El Hassane Anouar ◽

Mohamed Marzouk ◽

Mizaton H. Hasan ◽

Siti R. Saleh ◽

...

Keyword(s):

Molecular Docking ◽

Kojic Acid ◽

Docking Studies ◽

Breast Adenocarcinoma ◽

Amino Acid Residues ◽

New Class ◽

Structure Activity ◽

Tyrosinase Inhibitors ◽

Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Download Full-text

Synthesis of Novel Compounds as New Potent Tyrosinase Inhibitors

BioMed Research International ◽

10.1155/2013/207181 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Hooshang Hamidian

Keyword(s):

Kojic Acid ◽

Azo Compounds ◽

The Novel ◽

Mushroom Tyrosinase ◽

Reference Standard ◽

Tyrosinase Inhibition ◽

H Nmr ◽

Ft Ir ◽

Tyrosinase Inhibitors ◽

C Nmr

In the present paper, we report the synthesis and pharmacological evaluation of a new series of azo compounds with different groups (1-naphthol, 2-naphthol, andN,N-dimethylaniline) and trifluoromethoxy and fluoro substituents in the scaffold. All synthesized compounds (5a–5f) showed the most potent mushroom tyrosinase inhibition (IC50values in the range of 4.39 ± 0.76–1.71 ± 0.49 µM), comparable to the kojic acid, as reference standard inhibitor. All the novel compounds were characterized by FT-IR,1H NMR,13C NMR, and elemental analysis.

Download Full-text

Experimental and theoretical charge density analysis of skin whitening agent kojic acid

Journal of Molecular Structure ◽

10.1016/j.molstruc.2020.128295 ◽

2020 ◽

Vol 1216 ◽

pp. 128295

Author(s):

Asma Hasil ◽

Arshad Mehmood ◽

Sajida Noureen ◽

Maqsood Ahmed

Keyword(s):

Charge Density ◽

Kojic Acid ◽

Skin Whitening ◽

Whitening Agent ◽

Density Analysis

Download Full-text

Quantitative Determination of α-Arbutin, β-Arbutin, Kojic Acid, Nicotinamide, Hydroquinone, Resorcinol, 4-Methoxyphenol, 4-Ethoxyphenol, and Ascorbic Acid from Skin Whitening Products by HPLC-UV

Journal of AOAC International ◽

10.5740/jaoacint.14-123 ◽

2015 ◽

Vol 98 (1) ◽

pp. 5-12 ◽

Cited By ~ 16

Author(s):

Yan-Hong Wang ◽

Cristina Avonto ◽

Bharathi Avula ◽

Mei Wang ◽

Diego Rua ◽

...

Keyword(s):

Ascorbic Acid ◽

Kojic Acid ◽

Single Injection ◽

Solvent System ◽

Reversed Phase ◽

Skin Whitening ◽

Ph Values ◽

Different Types ◽

The Stability

Abstract An HPLC-UV method was developed for the quantitative analysis of nine skin whitening agents in a single injection. These compounds are α-arbutin, β-arbutin, kojic acid, nicotinamide, resorcinol, ascorbic acid, hydroquinone, 4-methoxyphenol, and 4-ethoxyphenol. The separation was achieved on a reversed-phase C18 column within 30 min. The mobile phase was composed of water and methanol, both containing 0.1% acetic acid (v/v). The stability of the analytes was evaluated at different pH values between 2.3 and 7.6, and the extraction procedurewas validated for different types of skin whitening product matrixes, which included two creams, a soap bar, and a capsule. The best solvent system for sample preparation was 20 mM NaH2PO4 containing 10% methanol at pH 2.3. The analytica method was validated for accuracy, precision, LOD, and LOQ. The developed HPLC-UV method was applied forthe quantitation of the nine analytes in 59 skin whitening products including creams, lotions, sera, foams, gels, mask sheets, soap bars, tablets, and capsules.

Download Full-text

Isoprenylated Phenolic Compounds from Morus macroura as Potent Tyrosinase Inhibitors

Planta Medica ◽

10.1055/s-0043-121698 ◽

2017 ◽

Vol 84 (05) ◽

pp. 336-343 ◽

Cited By ~ 7

Author(s):

Yifan Wang ◽

Liangjin Xu ◽

Wen Gao ◽

Lixin Niu ◽

Chunyue Huang ◽

...

Keyword(s):

Kojic Acid ◽

Positive Control ◽

Diels Alder ◽

Extensive Analysis ◽

Ic50 Value ◽

Ic50 Values ◽

Tyrosinase Inhibitors ◽

Inhibitory Activities ◽

New Compounds

AbstractThree new Diels-Alder adducts, macrourins E – G (1–3), one new 2-arylbenzofuran, macrourin H (4), and eight known Diels-Alder adducts (5–12) were isolated from Morus macroura. Their structures were elucidated through extensive analysis of spectroscopic data. The 1H NMR and ECD trends in the determination of the configurations of these Diels-Alder adducts were summarized. The tyrosinase inhibitory activities of all compounds isolated were evaluated, and the new compounds (1–4) as well as the eight known compounds (5–12) were found to be potent with IC50 values ranging from 0.39 to 4.54 µM. Among them, 1 showed the best tyrosinase inhibitory activity with an IC50 value of 0.39 µM, approximately 50 times stronger than the positive control, kojic acid.

Download Full-text

Development and validation of a new RP-HPLC method for the simultaneous determination of hydroquinone, kojic acid, octinoxate, avobenzone, BHA and BHT in skin-whitening cream

Analytical Methods ◽

10.1039/c5ay02207j ◽

2016 ◽

Vol 8 (5) ◽

pp. 1170-1180 ◽

Cited By ~ 10

Author(s):

Fanny Galimany-Rovira ◽

Pilar Pérez-Lozano ◽

Josep Ma Suñé-Negre ◽

Encarna García-Montoya ◽

Montserrat Miñarro ◽

...

Keyword(s):

Simultaneous Determination ◽

Kojic Acid ◽

Cost Effective ◽

Hplc Method ◽

Simultaneous Analysis ◽

Skin Whitening ◽

Rp Hplc ◽

Development And Validation

Simultaneous analysis with a single HPLC run allows for a much more cost-effective and less time-consuming analysis of skin-whitening cream.

Download Full-text

Hairy root culture of white mulberry (Morus alba L.) for a source of tyrosinase inhibitors

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2020.8611 ◽

2020 ◽

Vol 93 (1) ◽

Author(s):

Hanh Thi My Nguyen ◽

Tan Quoc Tran ◽

Anh Lan Bui ◽

Phuong Ngo Diem Quach

Keyword(s):

Agrobacterium Rhizogenes ◽

Hairy Root ◽

Hairy Roots ◽

Root Culture ◽

Hairy Root Culture ◽

Morus Alba ◽

Root Induction ◽

Skin Whitening ◽

Tyrosinase Inhibitors ◽

White Mulberry

White mulberry (Morus alba L.) root was reported to contain potential tyrosinase inhibitors such as norartocarpetin, streppogenin, oxyresveratrol (5, 7, 2′, 4′-tetrahydroxy-flavavone) and 2-arylbenzofuran. This study aims at investigating Morus alba L. hairy root culture to create a source of tyrosinase inhibitors for skin-whitening application. Morus alba L. leaf (including mesophyll and petiole) and stem explants were randomly wounded and inoculated with Agrobacterium rhizogenes ATCC 15834 in 10-40 minutes, and coculturing for 4 days. After inoculation, Agrobacterium rhizogenes were removed by using MS medium adding 200mg/L cefotaxime as antibiotics. Then, fresh inducted hairy roots were grown in nonphytohormone liquid medium (MS, White, Gamborg B5 or WPM) on a shaker (80rpm) at 25 ±1°C. Inducted hairy roots were tested for the present of rolB by PCR analysis and its effect on tyrosinase activity using a 96-well plate reader. The suitable explants for hairy root induction are leaves, especially petioles in 10 minutes (root induction frequency: 83%). After induction, hairy roots on MS was grown more efficiently (increased 3.933 times in FW) than on WPM, B5 and White medium. Inducted hairy roots were successfully transgenes by the present of rolB in their genome and had the same anti-tyrosinase activity as the natural roots without significance differences (IC50: 3.860 and 3.597 μg/mL, respectively). Cultured Morus alba L. hairy roots are potential source of tyrosinase inhibitors for future skin-whitening ingredient.

Download Full-text

BCl3 Catalyzed, Solvent Free Protocol For The Synthesis Of Dihydropyrano[3,2-b]chromenediones

Letters in Organic Chemistry ◽

10.2174/1570178617999200805163909 ◽

2020 ◽

Vol 17 ◽

Author(s):

Vikas B Suryawanshi ◽

Kalimoddin I Momin ◽

Jairaj K Dawle ◽

Sushil R Mathapati

Keyword(s):

Kojic Acid ◽

Aromatic Aldehydes ◽

Solvent Free ◽

Simple Reaction ◽

Alternative Method ◽

Short Period ◽

Efficient Alternative ◽

High Yields ◽

Solvent Free Synthesis

: Solvent free synthesis of dihydropyrano[3,2-b]chromenediones was formulated via multi-component reactions of kojic acid, dimedone and several substituted aromatic aldehydes catalyzed with BCl3. Reactions progressed efficiently and the corresponding heterocyclic products were obtained in good to high yields within short period. The developed protocol is one of the better and efficient alternative method for synthesis of dihydropyrano[3,2-b]chromenediones. The simple reaction procedure, easy separation of products, radially available catalyst are certain benefits of this reported protocol.

Download Full-text