JMB :: Journal of Microbiology and Biotechnology

Author	Hyun Woo Lee, Hansol Choi, Sang-Jip Nam, William Fenical, Hoon Kim
Place of duty	Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea
Title	Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp. CNQ-027
PublicationInfo	J. Microbiol. Biotechnol.2017 ; Vol.27-4
Abstract	Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1- oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an IC50 value of 1.21 μM; in addition, it was found to be highly effective against MAO-A, with an IC50 value of 6.47 μM. Compound 1 was selective, but not extremely so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8- dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately effective for the inhibition of MAO-B (IC50 = 14.50 μM) but not for MAO-A (IC50 > 80 μM). There was no time-dependency in inhibition of MAO-A or -B by compound 1, and the MAO-A and -B activities were almost completely recovered in the dilution experiments with an excess amount of compound 1. Compound 1 showed competitive inhibition for MAO-A and -B, with Ki values of 0.573 and 0.248 μM, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful lead compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson’s disease, and Alzheimer’s disease.
Full-Text
Key_word	Monoamine oxidase, piloquinone, Streptomyces sp. CNQ-027, potent selective inhibitor, competitive inhibitor

References

Ramsay RR. 2012. Monoamine oxidases: the biochemistry of the proteins as targets in medicinal chemistry and drug discovery. Curr. Top. Med. Chem. 12: 2189-2209.
Orhan IE. 2016. Potential of natural products of herbal origin as monoamine oxidase inhibitors. Curr. Pharm. Des. 22: 268-276.
Riederer P, Lachenmayer L, Laux G. 2004. Clinical applications of MAO-inhibitors. Curr. Med. Chem. 11: 2033-2043.
Youdim MB, Edmondson D, Tipton KF. 2006. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci. 7: 295-309.
Mostert S, Petzer A, Petzer JP. 2015. Indanones as high-potency reversible inhibitors of monoamine oxidase. ChemMedChem 10: 862-873.
Carradori S, Gidaro MC, Petzer A, Costa G, Guglielmi P, Chimenti P, et al. 2016. Inhibition of human monoamine oxidase: biological and molecular modeling studies on selected natural flavonoids. J. Agric. Food Chem. 64: 9004-9011.
Chaurasiya ND, Gogineni V, Elokely KM, León F, Núñez MJ, Klein ML, et al. 2016. Isolation of acacetin from Calea urticifolia with inhibitory properties against human monoamine oxidase-A and -B. J. Nat. Prod. 79: 2538-2544.
Ramsay RR. 2016. Molecular aspects of monoamine oxidase B. Prog. Neuropsychopharmacol. Biol. Psychiatry 69: 81-89.
Van der Walt MM, Terre’Blanche G, Petzer JP, Petzer A. 2017. Benzyloxynitrostyrene analogues - a novel class of selective and highly potent inhibitors of monoamine oxidase B. Eur. J. Med. Chem. 125: 1193-1199.
Fajemiroye JO, da Silva DM, de Oliveira DR, Costa EA. 2016. Treatment of anxiety and depression: medicinal plants in retrospect. Fundam. Clin. Pharmacol. 30: 198-215.
Mathew B, Suresh J, Mathew GE, Parasuraman R, Abdulla N. 2014. Plant secondary metabolites - potent inhibitors of monoamine oxidase isoforms. Cent. Nerv. Syst. Agents Med. Chem. 14: 28-33.
Carradori S, D’Ascenzio M, Chimenti P, Secci D, Bolasco A. 2014. Selective MAO-B inhibitors: a lesson from natural products. Mol. Divers. 18: 219-243.
Takeuchi T, Ogawa K, Iinuma H, Suda H, Ukita K, Nagatsu T, et al. 1973. Monoamine oxidase inhibitors isolated from fermented broths. J. Antibiot. 26: 162-167.
Lee IK, Yun B S, Oh S, K im Y H, L ee MK, Y oo ID. 19 9 9. 5-Methylmellein and nectriapyrone, two new monoamine oxidase inhibitors. Med. Sci. Res. 27: 463-465.
Lee HW, Jung WK, Kim HJ, Jeong YS, Nam SJ, Kang H, Kim H. 2015. Inhibition of monoamine oxidase by anithiactins from Streptomyces sp. J. Microbiol. Biotechnol. 25: 1425-1428.
Lee HW, Kim YJ, Nam SJ, Kim H. 2016. Potent selective inhibition of monoamine oxidase A by alternariol monomethyl ether isolated from Alternaria brassicae. J. Microbiol. Biotechnol. 27: 316-320.
Fenical W, Jensen PR. 2006. Developing a new resource for drug discovery: marine actinomycete bacteria. Nat. Chem. Biol. 2: 666-673.
Nam SJ, Kauffman CA, Jensen PR, Fenical W. 2011. Isolation and characterization of actinoramides A-C, highly modified peptides from a marine Streptomyces sp. Tetrahedron 67:6707-6712.
Gaudemer A, Polonsky J. 1964. Nuclear magnetic resonance of piloquinone and its derivatives. Bull. Soc. Chim. Fr. 8:1918-1923.
Polonsky J, Lederer E. 1963. Piloquinone: a new phenanthreneO-quinone isolated from the mycelium of Streptomyces pilosus. Nature 199: 285-286.
Jokela R, Lounasmaa M. 1997. Complete 1H- and 13C-NMR spectral data of piloquinone, a 9,10-phenanthrenequinone derivative from Streptomyces pilosus. Planta Med. 63: 85-86.
Legoabe LJ, Petzer A, Petzer JP. 2012. Inhibition of monoamine oxidase by selected C6-substituted chromone derivatives. Eur. J. Med. Chem. 49: 343-353.
Petzer A, Harvey BH, Petzer JP. 2014. The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase. Toxicol. Appl. Pharmacol. 274: 488493.
Lee MK, Hwang BY, Lee SA, Oh GJ, Choi WH, Hong SS, et al. 2003. 1-Methyl-2-undecyl-4(1H)-quinolone as an irreversible and selective inhibitor of type B monoamine oxidase. Chem. Pharm. Bull. (Tokyo) 51: 409-411.
Kong LD, Cheng CH, Tan RX. 2004. Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones. J. Ethnopharmacol. 91: 351-355.
Choi WH, Hong SS, Lee SA, Han XH, Lee KS, Lee MK, et al. 2005. Monoamine oxidase inhibitory naphthoquinones from the roots of Lithospermum erythrorhizon. Arch. Pharm. Res. 28:400-404.
Lee HW, Ryu HW, Kang MG, Park D, Oh SR, Kim H. 2016. Potent selective monoamine oxidase B inhibition by maackiain, a pterocarpan from the roots of Sophora flavescens. Bioorg. Med. Chem. Lett. 26: 4714-4719.