Kojic Acid (kojic + acid)

Distribution by Scientific Domains
Distribution within Chemistry


Selected Abstracts


Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives

ARCHIV DER PHARMAZIE, Issue 3 2010
Mutlu Dilsiz Aytemir
Abstract A series of new 3-hydroxy-6-hydroxymethyl/methyl-2-substituted 4H -pyran-4-ones were synthesized and prepared by the reaction of kojic acid or allomaltol with piperidine derivatives and formaline as potential anticonvulsant compounds. The structure of the synthesized compounds was confirmed using the elemental analysis results and the spectroscopic techniques such as IR, 1H-NMR, and ESI-MS. Anticonvulsant activities were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet)-induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies and at all doses, 3-hydroxy-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-6-methyl-4H -pyran-4-one (compound 1), 2-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]methyl}-3-hydroxy-6-methyl-4H -pyran-4-one (compound 6), 2-[(4-acetyl-4-phenylpiperidin-1-yl)methyl]-3-hydroxy-6-(hydroxymethyl)-4H -pyran-4-one (compound 11), and 2-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl] methyl}-3-hydroxy-6-hydroxymethyl-4H -pyran-4-one (compound 12) were found to have anticonvulsant activity against MES-induced seizures at 4 h. Also, 2-{[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]methyl}-3-hydroxy-6-(hydroxymethyl)-4H -pyran-4-one (compound 8) was determined to be the most active compound against scMet-induced seizures at all doses at 0.5 and 4 h. In the rotorod neurotoxicity screening, all compounds showed no toxicity at all doses. [source]


Kojic acid reduces the cytotoxic effects of sulfur mustard on cultures containing human melanoma cells in vitro

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2001
C. N. Smith
Abstract In vivo experiments have shown that melanocytes are more sensitive than keratinocytes to the cytotoxic effects of sulfur mustard when it is applied topically to pig skin.1 It has been hypothesized that this is caused by the uncoupling of the melanogenic pathway by depletion of cellular glutathione, resulting in the uncontrolled production of cytotoxic quinone free-radical species by tyrosinase.2. In the present study, the feasibility of blocking the melanogenic pathway as a means of reducing the cytotoxicity of sulfur mustard was evaluated using kojic acid. Kojic acid is a topically applied depigmenting agent that exerts its effect by acting as a slow-binding, competitive inhibitor of tyrosinase.3 Preincubation of G361 pigmented melanoma cells and mixed cultures of G361 cells and SVK keratinocytes with 2.5 mM kojic acid resulted in significant increases in the viability of these cultures as determined by neutral red (NR) and gentian violet (GV) dye binding assays for up to 48 h following exposure to 50 µM sulfur mustard. The highest levels of protection were seen in the G361 cultures, with a 26.8% increase in culture viability (NR assay) compared with the sulfur-mustard-only controls at 24 h. Preincubation of SVK cells alone with kojic acid resulted in lower increases in viability (2.5% at 24 h by the NR assay). Inhibition of the melanogenic pathway reduces the sensitivity of cultures containing pigment cells to sulfur mustard. © Crown copyright 2001. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [source]


Skin lightening preparations and the hydroquinone controversy

DERMATOLOGIC THERAPY, Issue 5 2007
Zoe Diana Draelos
ABSTRACT:, Skin lightening preparations are widely used in dermatology by persons of all Fitzpatrick skin types. Fitzpatrick skin types I,III require local pigment lightening for the treatment of hormonally induced melasma and postinflammatory hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker have an even greater need for skin lightening for social reasons, as well as pigmentary changes that occur around the eyes, in the intertriginous areas, following dermatitis, or with acne and trauma. The gold standard dermatologic agent for skin lightening was hydroquinone, until regulatory agencies in Japan, Europe, and most recently in the United States questioned the safety of this substance. This has encouraged research into alternative agents to inhibit skin pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid, aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine. The efficacy and safety of each of these ingredients is examined as possible topical alternatives to hydroquinone. [source]


Studying the anti-tyrosinase effect of Arbutus andrachne L. extracts

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2008
R. A. Issa
Synopsis Arbutus andrachne L. is widely distributed in Jordan. Tyrosinase is the key enzyme in the biosynthesis of melanin. This preliminary study was carried out to assess the possible anti-tyrosinase activity of A. andrachne extracts. Arbutin, hydroquinone and kojic acid were selected as inhibitor standards. Five different extracts (chloroform, butanol, ethanol, methanol and water) were prepared from A. andrachne stems and their activities were compared with the selected tyrosinase inhibitors. IC50 was measured for both, standard and plant extracts. Among the different extracts, the methanolic extract exhibited the highest anttyrosinase activity with an IC50 value (1 mg mL,1). Furthermore, 9 mg A. andrachne methanolic extract showed 97.49% inhibition of tyrosinase activity. Arbutin, hydroquinone, ,-sitosterol and ursolic acid were identified in the different extracts of A. andrachne by thin layer chromatography (TLC) and isolated by preparative TLC from the methanolic and chloroform stem extracts, respectively. Résumé Arbutus andrachne L. est largement répandu en Jordanie. La tyrosinase est un enzyme clé dans la biosynthèse de la mélanine. Cette étude préliminaire est menée dans le but de juger de la possible activité anti-tyrosinase des extraits d'A. andrachne L. L'arbutine, l'hydroquinone et l'acide kojique ont été sélectionnés comme inhibiteurs de référence. Cinq extraits différents (chloroforme, butanol, éthanol, méthanol et eau) ont été préparés à partir de tiges d'A. andrachne L. et leurs activités ont été comparées à celles des inhibiteurs de tyrosinase sélectionnés. L'IC50 a été mesurée à la fois pour les références et les extraits de plantes. Parmi les différents extraits, l'extrait méthanolique montre l'activité anti-tyrosinase la plus élevée avec une valeur d'IC50 de 1 mg mL,1. De plus, 9 mg d'extrait méthanolique d'A. andrachne L. possède une activité inhibitrice de la tyrosinase de 97.49%. L'arbutine, l'hydroquinone, le ,-sitostérol et l'acide ursolique ont été identifiés dans les différents extraits par chromatographie sur couches minces et isolés par chromatographie préparative, respectivement à partir des extraits méthanoliques et chloroformiques de tiges. [source]


Effect of different chemical compounds as coadjutants of 4-hexylresorcinol on the appearance of deepwater pink shrimp (Parapenaeus longirostris) during chilled storage

INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 11 2008
Oscar Martínez-Alvarez
Summary Different chemical compounds (kojic acid, cumic acid, phytic acid, sodium metabisulphite, magnesium carbonate, sorbic acid and different protease inhibitors) were used as coadjutants in 4-hexylresorcinol (4-HR)-based melanosis-inhibiting formulas tested for inhibiting melanosis in pink shrimp (Parapenaeus longirostris). The experiment was performed on board ship. Increasing concentrations of 4-HR delayed the occurrence of melanosis during storage. However, 4-HR could not prevent the appearance of a yellow-greenish colouration in the cephalothorax that diminishes the consumer acceptability of shrimps. The incorporation of protease inhibitors (ethylenediaminetetraacetic acid, disodium dihydrogen pyrophosphate, iodoacetic acid, egg white and phenylmethylsulphonyl fluoride) into the 4-HR-based mixtures improved the acceptability after storage, suggesting that protease activity post-mortem contributes to the reduction in the final acceptability of crustaceans. [source]


Kojic acid reduces the cytotoxic effects of sulfur mustard on cultures containing human melanoma cells in vitro

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2001
C. N. Smith
Abstract In vivo experiments have shown that melanocytes are more sensitive than keratinocytes to the cytotoxic effects of sulfur mustard when it is applied topically to pig skin.1 It has been hypothesized that this is caused by the uncoupling of the melanogenic pathway by depletion of cellular glutathione, resulting in the uncontrolled production of cytotoxic quinone free-radical species by tyrosinase.2. In the present study, the feasibility of blocking the melanogenic pathway as a means of reducing the cytotoxicity of sulfur mustard was evaluated using kojic acid. Kojic acid is a topically applied depigmenting agent that exerts its effect by acting as a slow-binding, competitive inhibitor of tyrosinase.3 Preincubation of G361 pigmented melanoma cells and mixed cultures of G361 cells and SVK keratinocytes with 2.5 mM kojic acid resulted in significant increases in the viability of these cultures as determined by neutral red (NR) and gentian violet (GV) dye binding assays for up to 48 h following exposure to 50 µM sulfur mustard. The highest levels of protection were seen in the G361 cultures, with a 26.8% increase in culture viability (NR assay) compared with the sulfur-mustard-only controls at 24 h. Preincubation of SVK cells alone with kojic acid resulted in lower increases in viability (2.5% at 24 h by the NR assay). Inhibition of the melanogenic pathway reduces the sensitivity of cultures containing pigment cells to sulfur mustard. © Crown copyright 2001. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd. [source]


Optimisation of kojic acid monolaurate synthesis with lipase PS from Pseudomonas cepacia

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 6 2002
Chee-Shan Chen
Abstract To improve the instability of kojic acid in food and cosmetic use, the esterification of kojic acid catalysed by lipase from Pseudomonas cepacia (Amano PS) to synthesise kojic acid monolaurate (KAML) was investigated in this study. Response surface methodology (RSM) with a five-level/five-factor central composite rotatable design (CCRD) was employed to evaluate the effects of synthesis parameters such as reaction time (8,24,h), temperature (35 55,°C), enzyme amount (10,50%), substrate molar ratio of lauric acid to kojic acid (1:1,3:1) and added water content (0,20%) on the percentage molar conversion to KAML by direct esterification. Reaction time and added water content were the most important variables, while substrate molar ratio had less effect on percentage molar conversion. Based on canonical analysis and ridge maximum analysis, optimal synthesis conditions were reaction time 19,h, temperature 44,°C, enzyme amount 38%, substrate molar ratio 2:1 and added water content 10%. The predicted value was 85% and the actual experimental value 82% molar conversion. © 2002 Society of Chemical Industry [source]


Tyrosinase inhibitory constituents from the stems of Maackia fauriei

PHYTOTHERAPY RESEARCH, Issue 1 2010
Jeong Mi Kim
Abstract Bioassay-guided investigation of the stems of Maackia fauriei led to the isolation of seven flavonoid constituents, formononetin (1), genistein (2), daidzein (3), texasin (4), tectorigenin (5), odoratin (6) and mirkoin (7). Their structures were elucidated on the basis of spectral studies as well as by comparison with literature data. Tyrosinase inhibition activities were carried out on the isolated compounds. Among these, mirkoin (7) was identified as a potent tyrosinase inhibitor. It inhibited mushroom tyrosinase with an IC50 value of 0.005,mm, which is ten times more active than kojic acid (IC50 = 0.045,mm). The inhibition kinetics, analysed by Lineweaver-Burk plots, indicated mirkoin (7) to be a competitive inhibitor of tyrosinase when l -tyrosinase was used as a substrate. The results suggest that hydroxyl groups at C-4, in the B ring of flavonoids play an important role in the tyrosinase inhibition activities. Interestingly, compounds 4,7 were isolated for the first time from this plant. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives

ARCHIV DER PHARMAZIE, Issue 3 2010
Mutlu Dilsiz Aytemir
Abstract A series of new 3-hydroxy-6-hydroxymethyl/methyl-2-substituted 4H -pyran-4-ones were synthesized and prepared by the reaction of kojic acid or allomaltol with piperidine derivatives and formaline as potential anticonvulsant compounds. The structure of the synthesized compounds was confirmed using the elemental analysis results and the spectroscopic techniques such as IR, 1H-NMR, and ESI-MS. Anticonvulsant activities were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet)-induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies and at all doses, 3-hydroxy-2-[(4-hydroxy-4-phenylpiperidin-1-yl)methyl]-6-methyl-4H -pyran-4-one (compound 1), 2-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl]methyl}-3-hydroxy-6-methyl-4H -pyran-4-one (compound 6), 2-[(4-acetyl-4-phenylpiperidin-1-yl)methyl]-3-hydroxy-6-(hydroxymethyl)-4H -pyran-4-one (compound 11), and 2-{[4-(4-chlorophenyl)-3,6-dihydropyridin-1(2H)-yl] methyl}-3-hydroxy-6-hydroxymethyl-4H -pyran-4-one (compound 12) were found to have anticonvulsant activity against MES-induced seizures at 4 h. Also, 2-{[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]methyl}-3-hydroxy-6-(hydroxymethyl)-4H -pyran-4-one (compound 8) was determined to be the most active compound against scMet-induced seizures at all doses at 0.5 and 4 h. In the rotorod neurotoxicity screening, all compounds showed no toxicity at all doses. [source]


Synthesis of Tyrosinase Inhibitory Kojic Acid Derivative

ARCHIV DER PHARMAZIE, Issue 3 2006
Yong Sup Lee
Abstract Kojic acid derivative 2 was synthesized by joining two pyrone rings through an ethylene linkage by Horner-Emmons reaction of phosphonate 6 with aldehyde 7. The intermediates 6 and 7 were derived from kojic acid. The tyrosinase inhibitory activity of 2 was about 8 times more potent (IC50 = 3.63 ,M) than that of kojic acid (IC50 = 30.61 ,M). Compound 2 also exhibited potent melanin synthesis inhibitory activity (19.53% inhibition at 5 ,g) indicating that the connection of two pyrone rings of kojic acid through a suitable linker can be an useful strategy for identification of potent tyrosinase inhibitiors. [source]


Prediction of Tyrosinase Inhibition Activity Using Atom-Based Bilinear Indices

CHEMMEDCHEM, Issue 4 2007
Yovani Marrero-Ponce Prof.
Abstract A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, Mk and Sk, respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using Mk and Sk as matrix operators of bilinear transformations. Chemical information is coded by using different pair combinations of atomic weightings (mass, polarizability, vdW volume, and electronegativity). The results of QSAR studies of tyrosinase inhibitors using the new MDs and linear discriminant analysis (LDA) demonstrate the ability of the bilinear indices in testing biological properties. A database of 246 structurally diverse tyrosinase inhibitors was assembled. An inactive set of 412 drugs with other clinical uses was used; both active and inactive sets were processed by hierarchical and partitional cluster analyses to design training and predicting sets. Twelve LDA-based QSAR models were obtained, the first six using the nonstochastic total and local bilinear indices and the last six with the stochastic MDs. The discriminant models were applied; globally good classifications of 99.58 and 89.96,% were observed for the best nonstochastic and stochastic bilinear indices models in the training set along with high Matthews correlation coefficients (C) of 0.99 and 0.79, respectively, in the learning set. External prediction sets used to validate the models obtained were correctly classified, with accuracies of 100 and 87.78,%, respectively, yielding C values of 1.00 and 0.73. This subset contains 180 active and inactive compounds not considered to fit the models. A simulated virtual screen demonstrated this approach in searching tyrosinase inhibitors from compounds never considered in either training or predicting series. These fitted models permitted the selection of new cycloartane compounds isolated from herbal plants as new tyrosinase inhibitors. A good correspondence between theoretical and experimental inhibitory effects on tyrosinase was observed; compound CA6 (IC50=1.32,,M) showed higher activity than the reference compounds kojic acid (IC50=16.67,,M) and L -mimosine (IC50=3.68,,M). [source]