Synthesis and biological evaluation of substituted aurone derivatives as potential tyrosinase inhibitors: in vitro, kinetic, QSAR, docking and drug-likeness studies.

Tyrosinase enzyme plays an essential role in melanin biosynthesis and enzymatic browning of fruits and vegetables. To discover potent tyrosinase inhibitors, the present studies were undertaken. In this context, synthetic aurone derivatives 26-50 were designed, synthesized, and structurally elucidated by various spectroscopic techniques including IR, UV, 1H- & 13C-NMR and mass spectrometry. The target compounds 26-50 were screened for their anti-tyrosinase inhibitory potential, and thus kinetic mechanism was analyzed by Lineweaver-Burk plots. All target compounds exhibited good to excellent IC50 values in the range of 7.12 ± 0.32 µM to 66.82 ± 2.44 µM. These synthesized aurone derivatives were found as potent tyrosinase inhibitors relative to the standard kojic acid (IC50 = 16.69 ± 2.81 µM) and the compound 39 inhibited tyrosinase non-competitively (Ki = 11.8 µM) by forming an enzyme-inhibitor complex. The binding modes of these molecules were ascribed through molecular docking studies against tyrosinase protein (PDB ID: 2Y9X). The quantitative structure-activity relationship studies displayed a good correlation between 26-50 structures and their anti-tyrosinase activity (IC50) with a correlation coefficient (R2) of 0.9926. The computational studies were coherent with experimental results and these ligands exhibited good binding values against tyrosinase and interacted with core residues of target protein. Moreover, the drug-likeness analysis also showed that some compounds have a linear correlation with Lipinski's rule of five, indicating good drug-likeness and bioactivity scores for pharmacological targets.Communicated by Ramaswamy H. Sarma.

Hyponatremia Associated With Standard-Dose Trimethoprim-Sulfamethoxazole Use in an Immunocompetent Patient.

INTRODUCTION: Trimethoprim-sulfamethoxazole (TMP-SMX) use in immunocompromised patients can cause dose-dependent electrolyte irregularities including hyponatremia, hyperkalemia, and metabolic acidosis. We report a case of isolated hyponatremia caused by low-dose TMP-SMX use in an immunocompetent patient that mimicked the syndrome of inappropriate antidiuretic hormone secretion (SIADH). CASE PRESENTATION: A 72-year-old woman was admitted to the hospital for acute onset of weakness and ambulatory dysfunction after starting TMP-SMX (160 mg/800 mg). She was found hyponatremic (sodium level, 125 mmol/L, down from 141 mmol/L prior to medication initiation). After ruling out diuretics use, and adrenal and thyroid dysfunction, we started her on intravenous saline infusion to manage her TMP-SMX-induced hyponatremia, and her symptoms resolved. DISCUSSION: Electrolyte problems in immunocompromised patients treated for opportunistic infections with high-dose TMP-SMX (≥ 8 mg/kg/d TMP) are well-documented. However, the effects in immunocompetent patients are uncommon when standard dose (< 8 mg/kg/d TMP) is used. CONCLUSIONS: TMP-SMX blocks the aldosterone-mediated sodium reabsorption in the collecting ducts, and the trimethoprim component itself is structurally similar to potassium-sparing diuretics, which block sodium uptake at the distal nephron-both of which can cause hyponatremia.

DDQ as a versatile and easily recyclable oxidant: a systematic review.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is the most widely used quinone with a high reduction potential, and it commonly mediates hydride transfer reactions and shows three accessible oxidation states: quinone (oxidized), semiquinone (one-electron-reduced), and hydroquinone (two-electron-reduced). DDQ has found broad utility as a stoichiometric oxidant in the functionalization of activated C-H bonds and the dehydrogenation of saturated C-C, C-O, and C-N bonds. The cost and toxicity of DDQ triggered recent efforts to develop methods that employ catalytic quantities of DDQ in combination with alternative stoichiometric oxidants. The aerobic catalytic approach was established for the selective oxidation of non-sterically hindered electron-rich benzyl methyl ethers and benzylic alcohols, and effectively extended to the oxidative deprotection of p-methoxybenzyl ethers to generate the alcohols in high selectivity. A combination of DDQ and protic acid is known to oxidize several aromatic donors to the corresponding cation radicals. The excited-state DDQ converts benzyls, heteroarenes, fluoroarenes, benzene, and olefins into their radical cation forms as well as chloride and other anions into their respective radicals. These reactive intermediates have been employed for the generation of C-C and C-X (N, O, or Cl) bonds in the synthesis of valuable natural products and organic compounds. To the best of our knowledge, however, there is still no review article exclusively describing the applications of DDQ in organic synthesis. Therefore, in the present review, we provide an overview of DDQ-induced organic transformations with their scope, limitations and the proposed reaction mechanisms.