| Autor: |
Oh JM; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea., Jang HJ; Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea., Kang MG; Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea., Mun SK; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea., Park D; Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea., Hong SJ; Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea., Kim MH; National Institute of Biological Resources, Environmental Research Complex, Incheon 22689, Republic of Korea., Kim SY; National Institute of Biological Resources, Environmental Research Complex, Incheon 22689, Republic of Korea., Yee ST; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea., Kim H; Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea. |
| Abstrakt: |
Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC 50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13 . Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (K i = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13 . However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders. |
