1-1-diphenyl-2-picrylhydrazyl and kojic-acid

Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC

Topics: Animals; Antineoplastic Agents; Biological Products; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Mice; Molecular Docking Simulation; Molecular Structure; Monophenol Monooxygenase; Picrates; Pyrones; Quinazolinones; Structure-Activity Relationship; Sulfhydryl Compounds

The novel kojic acid derivatives KAD1 and KAD2 have been demonstrated that they exhibited potent anti-melanogenesis activity in our previous report. In this study, we further study the inhibitory mechanism on mushroom tyrosinase. The inhibitory types of both KADs on diphenolase were classified as mixed type based on the results of the kinetic model. The interaction between KADs and tyrosinase was illustrated by fluorescence quenching, molecular docking and copper chelate activity. The KADs were also evaluated with respect to their antioxidant activities by DPPH and ABTS

Topics: Agaricales; Antioxidants; Benzothiazoles; Biphenyl Compounds; Dose-Response Relationship, Drug; Enzyme Inhibitors; Kinetics; Molecular Docking Simulation; Monophenol Monooxygenase; Picrates; Pyrones; Spectrometry, Fluorescence; Structure-Activity Relationship; Sulfonic Acids

The purpose of this work was to develop a nontoxic bioactive material based on a natural pyrone compound (kojic acid, KA) and chitosan oligosaccharides (COS). The bioactive material, chitosan oligosaccharide-N-kojic acid polymer (COS-N-KA), was prepared by one-step environmentally friendly approach. Then, the physicochemical properties and biological activities of COS-N-KA as a prepared water-soluble COS derivative were evaluated. The polymer was characterized by using UV-vis, FTIR,

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Bacteria; Biphenyl Compounds; Chitosan; Hemolysis; Humans; Iron; Male; Mice; Picrates; Pyrones; Solubility; Structure-Activity Relationship

Topics: Agaricales; Animals; Biphenyl Compounds; Chick Embryo; Enzyme Inhibitors; Melanins; Melanoma, Experimental; Methimazole; Mice; Monophenol Monooxygenase; Picrates; Pyrones; Skin; Skin Neoplasms; Tumor Cells, Cultured

Ramalin (γ-glutamyl-N'-(2-hydroxyphenyl)hydrazide), a novel compound, was isolated from the methanol-water extract of the Antarctic lichen Ramalina terebrata by several chromatographic methods. The molecular structure of ramalin was determined by spectroscopic analysis. The experimental data showed that ramalin was five times more potent than commercial butylated hydroxyanisole (BHA) in scavenging 1-diphenyl-2-picryl-hydazil (DPPH) free radicals, 27 times more potent in scavenging 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid free radicals (ABTS(+)) than the vitamin E analogue, trolox, and 2.5 times more potent than BHT in reducing Fe(3+) to Fe(2+) ions. Similarly, ramalin was 1.2 times more potent than ascorbic acid in scavenging superoxide radicals and 1.25 times more potent than commercial kojic acid in inhibiting tyrosinase enzyme activity, which ultimately leads to whitening of skin cells. Ramalin showed no or very little cytotoxicity in human keratinocyte and fibroblast cells at its antioxidant concentration. Furthermore, ramalin was assessed to determine its antioxidant activity in vivo. One microgram per milliliter ramalin significantly reduced the released nitric oxide (NO) and 0.125 μg/ml ramalin reduced the produced hydrogen peroxide (H(2)O(2)) in LPS (lipopolysaccharide)-stimulated murine macrophage Raw264.7 cells. Considering all the data together, ramalin can be a strong therapeutic candidate for controlling oxidative stress in cells.

Topics: Animals; Antarctic Regions; Antioxidants; Ascorbic Acid; Benzothiazoles; Biphenyl Compounds; Butylated Hydroxyanisole; Cell Line; Cell Survival; Chromans; Fibroblasts; Free Radicals; Fungal Proteins; Glutamates; Humans; Hydrogen Peroxide; Keratinocytes; Lichens; Mice; Molecular Structure; Monophenol Monooxygenase; Nitric Oxide; Picrates; Pyrones; Sulfonic Acids

To investigate the stem bark of Sideroxylon inerme L. and its compounds for tyrosinase-inhibition activity and to evaluate the mechanism involved of the most potent compounds in tyrosinase inhibition.. Three different extracts (acetone, methanol and dichloromethane) of Sideroxylon inerme L. were evaluated for their inhibitory effect in vitro on the monophenolase and diphenolase activated forms of tyrosinase, using a colorimetric procedure. This test was used for bioactivity-guided isolation of two active compounds using column chromatography and TLC. Active extracts were also investigated for their inhibitory effect on melanogenesis in cultured B16 melanoma cells. Antioxidant activities of the methanolic extract of Sideroxylon inerme and purified compounds were investigated using the 1,2-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assay. The inhibition of tyrosinase activity relative to the inhibition of its activity at the transcriptional level was also studied by determination of the degree of expression of mRNAs for this gene by using extract of Sideroxylon inerme-treated cells (B16F10) and semi-quantitative RT-PCR.. Methanolic and acetonic extracts of the stem bark of Sideroxylon inerme showed significant inhibition of monophenolase activity (IC50 values of 63 microg/ml and 82 microg/ml, respectively). The methanolic extract also exhibited 37% reduction of melanin content at 6.2 microg/ml in melanocytes without being significantly toxic to the cells. Examination for inhibition of monophenoloxidase in situ on TLC, followed by column chromatographic purification of the stem bark extract of Sideroxylon inerme, resulted in the isolation of two active compounds, epigallocatechin gallate and procyanidin B1, with IC50 values against monophenolase of 30 microg/ml and > 200 microg/ml, respectively. Epigallocatechin gallate exhibited a greater anti-tyrosinase activity than arbutin. Sideroxylon inerme bark extracts, epigallocatechin gallate and procyanidin B1 exhibited antioxidant DPPH radical scavenging activities with EC50 values of 1.54 microg/ml, 1.33 microg/ml and 1.68 microg/ml, respectively and were not particularly cytotoxic. During mechanism studies it was evident that at the transcription level, Sideroxylon inerme (25 microg/ml) was acting as a potent tyrosinase inhibitor compared to controls (untreated cells and kojic acid).. The bark extract of Sideroxylon inerme and the two isolated compounds warrant further investigation in clinical studies to be considered as skin-depigmenting agents.

Topics: Animals; Antioxidants; Biphenyl Compounds; Cell Survival; Colorimetry; DNA Primers; Enzyme Inhibitors; Indicators and Reagents; Melanins; Melanocytes; Mice; Monophenol Monooxygenase; Picrates; Plant Bark; Plant Extracts; Plant Stems; Pyrones; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sapotaceae; Skin Pigmentation; South Africa

Novel hybrid L-ascorbic acid (vitamin C) derivatives with other biologically active substances, 5-hydroxy-2-hydroxymethyl-beta-pyrone (kojic acid) and alpha-tocopherol (vitamin E), linked at the C-2 or C-3 hydroxyl group were synthesized, and their thermal stability and inhibitory effects on tyrosinase activity, active oxygen species (AOS), and free radicals were estimated in vitro. It was found that a hydrophilic derivative, 2-O-(5-hydroxy-4H-pyran-4-one-2-methyl)-L-ascorbic acid (1), exhibited good thermal stability and inhibitory activities against tyrosinase catalyzed melanin formation, AOS, and free radicals compared to vitamin C and its conventional derivatives (such as the 2-phosphate 6-stearate and 2.6-dipalmitate, and 2-O-octadecylascorbic acid), as well as vitamin E, kojic acid, and arbutin. It is apparent that 1 has the biological properties of vitamin C and kojic acid, and acts synergistically. The hydroxyl groups at the C-3 position of the vitamin C moiety and the C-5 position of the kojic acid moiety are critical for the biological activities. We consider that the kojic acid moiety of 1 counterbalances the diminution of the biological activity due to shielding of the biologically important C-2 hydroxyl group of the vitamin C moiety. In addition, the thermal stability was significantly improved relative to not only vitamin C but also kojic acid. Further, a lipophilic derivative, 3-O-[(alpha-tocopheryloxy)-2-hydroxypropyl]-L-ascorbic acid, 2, was far more stable than vitamin C and its typical lipophilic derivatives. Compound 2 exhibited almost the same inhibitory activities against tyrosinase-catalyzed melanin formation, AOS, and free radicals as typical lipophilic derivatives, although these biological activities of 2 were lower than those of vitamin C.

Topics: Ascorbic Acid; Bepridil; Biphenyl Compounds; Free Radicals; Melanins; Monophenol Monooxygenase; Oxidation-Reduction; Photochemistry; Picrates; Pyrones; Reactive Oxygen Species; Superoxides; Temperature; Tyrosine; Vitamin E