Xia Likai, Idhayadhulla Akber, Lee Yong Rok, Wee Young-Jung, Kim Sung Hong
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Eur J Med Chem. 2014 Oct 30;86:605-12. doi: 10.1016/j.ejmech.2014.09.025. Epub 2014 Sep 9.
Novel 5-hydroxy-4-acetyl-2,3-dihydronaphtho[1,2-b]furans (7a-k) were synthesized using ceric ammonium nitrate (CAN)-catalyzed formal [3 + 2] cycloaddition. Synthesized compounds were evaluated for their tyrosinase inhibitory, antioxidant, and antibacterial activities. A modified spectrophotometric method using l-DOPA as substrate was used to determine tyrosinase inhibitory activities, and a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was used to evaluate antioxidant properties. Antibacterial activities against gram-negative Escherichia coli (KCTC-1924) and gram-positive Staphylococcus aureus (KCTC-1916) were evaluated using the disc diffusion technique. Of the synthesized compounds, 7b with a 4-acetyl and an electron-enriched dihydronaphthofuran ring showed the highest tyrosinase-inhibition activity (IC50 = 8.91 μg/mL), which was comparable with that of standard kojic acid (IC50 = 10.16 μg/mL), potent antioxidant activity (IC50 = 3.33 μg/mL), which was comparable with that of BHT (IC50 = 34.67 μg/mL), and excellent antibacterial activities (MICs: 0.50 μg/mL against E. coli and S. aureus strains). A mechanistic analysis of 7b demonstrated that its tyrosinase inhibitory activity was reversible and competitive. Compounds 7c and 7d showed potent antioxidant activities (IC50: 6.30 and 5.01 μg/mL), and compound 7d also exhibited potent inhibitory activity against E. coli with a MIC of 0.5 μg/mL. Furthermore, compounds 7a, 7e, 7f, and 7i showed potent antibacterial activities against S. aureus with MICs of 0.5 μg/mL, which was comparable to that of ampicillin (MIC = 0.5 μg/mL).
使用硝酸铈铵（CAN）催化的形式[3 + 2]环加成反应合成了新型5-羟基-4-乙酰基-2,3-二氢萘并[1,2 - b]呋喃（7a - k）。对合成的化合物进行了酪氨酸酶抑制、抗氧化和抗菌活性评估。采用以L - 多巴为底物的改良分光光度法测定酪氨酸酶抑制活性，并用1,1 - 二苯基 - 2 - 苦基肼（DPPH）法评估抗氧化性能。使用纸片扩散法评估对革兰氏阴性大肠杆菌（KCTC - 1924）和革兰氏阳性金黄色葡萄球菌（KCTC - 1916）的抗菌活性。在合成的化合物中，具有4 - 乙酰基和富电子二氢萘并呋喃环的7b表现出最高的酪氨酸酶抑制活性（IC50 = 8.91μg/mL），与标准曲酸（IC50 = 10.16μg/mL）相当，具有较强的抗氧化活性（IC50 = 3.33μg/mL），与丁基羟基甲苯（BHT，IC50 = 34.67μg/mL）相当，并且具有优异的抗菌活性（MIC：对大肠杆菌和金黄色葡萄球菌菌株均为0.50μg/mL）。对7b的机理分析表明其酪氨酸酶抑制活性是可逆且具有竞争性的。化合物7c和7d表现出较强的抗氧化活性（IC50：6.30和5.01μg/mL），化合物7d对大肠杆菌也表现出较强的抑制活性，MIC为0.5μg/mL。此外，化合物7a、7e、7f和7i对金黄色葡萄球菌表现出较强的抗菌活性，MIC为0.5μg/mL，与氨苄西林（MIC = 0.5μg/mL）相当。
