链黑菌素研究进展
|
摘要
链黑菌素(streptonigrin,STN)是一种由绒毛链霉菌(Streptomyces flocculus)产生的具有独特的氨基喹啉醌式结构的高效抗肿瘤抗生素,在癌症治疗方面具有良好的防治效果和广阔的应用前景。但是,由于链黑菌素具有较为显著的骨髓抑制副作用,限制了其在临床上的广泛应用。综述了有关链黑菌素的抗肿瘤机制、结构特点及链黑菌素及其类似物生物化学合成相关的现有知识和减除毒副作用的研究现状与展望,从而为开发低毒、无毒副作用的链黑菌素及其类似物提供科学参考。
Streptonigrin(STN) is an anti-tumor antibiotic with a unique aminoquinolinium structure produced by Streptomyces flocculus,which has good control effect and broad application prospects in cancer treatment. However,the clinical application of STN has been limited because of its relatively significant myelosuppression side effect. The anti-tumor mechanism,structural features and existing knowledge related to the biosynthesis of streptonigrin and its analogs,including research status and prospects of reducing toxic side effects have been summarized,and providing a scientific reference for the development of low or non-toxic streptonigrin and its analogues.
Streptonigrin(STN) is an anti-tumor antibiotic with a unique aminoquinolinium structure produced by Streptomyces flocculus,which has good control effect and broad application prospects in cancer treatment. However,the clinical application of STN has been limited because of its relatively significant myelosuppression side effect. The anti-tumor mechanism,structural features and existing knowledge related to the biosynthesis of streptonigrin and its analogs,including research status and prospects of reducing toxic side effects have been summarized,and providing a scientific reference for the development of low or non-toxic streptonigrin and its analogues.
引文
[1]Qian T L,Wo J,Zhang Y,et al.Crystal structure of StnA for the biosynthesis of antitumor drug streptonigrin reveals a unique substrate binding mode.Scientific Reports,2017,7:40254.
[2]Heikal A,Hards K,Cheung C Y,et al.Activation of type II NADHdehydrogenase by quinolinequinones mediates antitubercular cell death.Journal of Antimicrobial Chemotherapy,2016,71(10):2840-2847.
[3]Kadela-Tomanek M,Pawelczak B,Jastrzgbska M,et al.Structural,vibrational and quantum chemical investigations for 6,7dichloro-2-methyl-5,8-quinolinedione.Cytotoxic and molecular docking studies.Journal of Molecular Structure,2018,1168:73-83.
[4]Testoni M I,Bolzán A D,Bianchi M S,et al.Effects of antioxidants on streptonigrin-induced DNA damage and clastogenesis in CHOcells.Mutation Research,1997,373(2):201-206.
[5]Testoni M I,Bianchi N O,Bianchi M S.The kinetics of chromosome and DNA damage by streptonigrin in CHO cells.Mutation Research,1995,334(1):23-31.
[6]Andersson R C.Induction of sister-chromatid exchanges by streptonigrin,an antibiotic and antineoplastic agent.Hereditas,1981,95(1):141-148.
[7]DuFrain R J,Littlefield L G,Morrison W D,et al.Evaluation of chemically induced cytogenetic lesions in rabbit oocytes.III.Apost-implantation analysis of streptonigrin effects.Mutation Research,1984,127(1):73-79.
[8]Cadieux B,Colavecchio A,Jeukens J,et al.Prophage induction reduces shiga toxin producing Escherichia coli(STEC)and salmonella entericaon tomatoes and spinach:a model study.Food Control,2018,89:250-259.
[9]Cone R,Hasan S,Lown J.The mechanism of the degradation of DNA by streptonigrin.Canadian Journal of Biochemistry,1976,54(3):219-223.
[10]Rao K V,Cullen W P.Streptonigrin,an antitumor substance.I.Isolation and characterization.Antibiotics Annual,1959,2010(3):950-953.
[11]Brazhnikova M G,Ponomarenko V I,Kovsharova I N,et al.Study on bruneomycin produced by act.albus var.Bruneomycini and its identification with streptonigrin.Antibiot Khimioter,1968,13(2):99-102.
[12]Malkina N D,DudnikIu V,Lysenkova L N,et al.Induction of antibiotic formation by inactive cultures of actinomycetes.Amutant strain of Streptomyces helvaticus,a new producer of bruneomycin.Antibiot Khimioter,1995,40(6):3-6.
[13]Wang H S,Yeo S L,Xu J,et al.Isolation of streptonigrin and its novel derivative from Micromonospora as inducing agents of p53-dependent cell apoptosis.Journal of Natural Products,2002,65(5):721-724.
[14]Jin Y Y,Yoon T M,Kim W K,et al.Kitasatospora sp.MJM383strain producing two antitumor agents,streptonigrin and oxopropaline G.Journal of Microbiology and Biotechnology,2005,15(5):1140-1145.
[15]Sugiura Y,Kuwahara J,Suzuki T.DNA interaction and nucleotide sequence cleavage of copper-streptonigrin.Biochimicaet Biophysica Acta,1984,782(3):254-261.
[16]Anderberg P I,Harding M M.The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin.Journal of Inorganic Biochemistry,2004,98(5):720-726.
[17]Yamashita Y,Kawada S,Fujii N,et al.Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin.Cancer Research,1990,50(18):5841-5844.
[18]Gavriil M,Tsao C C,Mandiyan S,et al.Specific IKK beta inhibitor IV blocks streptonigrin-induced NF-kappa B activity and potentiates its cytotoxic effect on cancer cells.Molecular Carcinogenesis,2009,48(8):678-684.
[19]Beall H D,Murphy A M,Siegel D,et al.Nicotinamide adenine dinucleotide(phosphate):quinoneoxidoreductase(DT-diaphorase)as a target for bioreductive antitumor quinones:quinone cytotoxicity and selectivity in human lung and breast cancer cell lines.Molecular Pharmacology,1995,48(3):499-504.
[20]Cohen M M,Shaw M W,Craig A P.The effects of streptonigrin on cultured human leukocytes.Proceedings of the National Academy of Sciences,1963,50(50):16-24.
[21]Sanchez J,Bianchi M S,Ciancio V R,et al.Analysis of spontaneous and streptonigrin-induced sister chromatid exchanges in peripheral iymphocytes of aircrew members of international flights.Journal of Environmental Pathology Toxicology and Oncology,2008,27(4):277-285.
[22]Mencucci M V,Bravo M V,Bianchi M S,et al.Streptonigrin induces delayed chromosomal instability involving interstitial telomeric sequences in chinese hamster ovary cells.Mutation Research-Genetic Toxicology and Environmental Mutagenesis,2012,747(1):46-52.
[23]Dreyton C J,Anderson E D,Subramanian V,et al.Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation.Bioorganic&Medicinal Chemistry,2014,22(4):1362-1369.
[24]Park S,Chun S.Streptonigrin inhibits beta-Catenin/Tcf signaling and shows cytotoxicity in beta-catenin-activated cells.Biochimicaet Biophysica Acta,2011,1810(12):1340-1345.
[25]Khandoga N,Pohl U.Gap junction communications promote streptonigrin-induced apoptosis in He La cells.Journal of Vascular Research,2006,43(1):50.
[26]Ambaye N,Chen C H,Khanna S,et al.Streptonigrininhibits SENP1 and reduces the protein level of hypoxia-inducible factor 1alpha(HIF1 alpha)in cells.Biochemistry,2018,57(11):1807-1813.
[27]Lewis A M,Ough M,Du J,et al.Targeting NAD(P)H:quinoneoxidoreductase(nqo1)pancreatic cancer.Molecular Carcinogenesis,2017,56(7):215-224.
[28]Gavriil M,Tsao C C,Mandiyan S,et al.Specific IKK beta inhibitor IV blocks streptonigrin-induced NF-kappa B activity and potentiates its cytotoxic effect on cancer cells.Molecular Carcinogenesis,2009,48(8):678-684.
[29]Gutteridge J M.Streptonigrin-induced deoxyribosedegradation:inhibition by superoxide dismutase,hydroxylradical scavengers and ironchelators.Biochemical Pharmacology,1984,33(19):3059-3062.
[30]Krishna M C,Halevy R F,Zhang R,et al.Modulation of streptonigrincytotoxicitybynitroxide SOD mimics.Free Radical Biology&Medicine,1994,17(5):379-388.
[31]De Graff W,Hahn S M,Mitchell J B,et al.Free radical modes of cytotoxicity of adriamycinandstreptonigrin.Biochemical Pharmacology,1994,48(7):1427-1435.
[32]Kadela-Tomanek M,Jastrzebska M,Bebenek E,et al.Newacetylenic amine derivatives of 5,8-quinolinediones:synthesis,crystal structure and antiproliferative activity.Crystals,2017,7(1):15.
[33]Rao K V,Biemann K,Woodward R B.The structure of streptonigrin.Journal of The American Chemical Society.1963,85(16):2532-2533.
[34]Bringmann G,Reichert M,Hemberger Y.The absolute configuration of streptonigrin.Tetrahedron,2008,64(3):515-521.
[35]Gould S J,Chang C C.Streptonigrinbiosynthesis.1.origin of the 4-phenylpicolinic acid moiety.Journal of The American Chemical Society,1977,99(16):5496-5497.
[36]Gould S J,Darling D S.Streptonigrin biosynthesis.2.the isolation ofβ-methyltryptophanand its intermediacy in the streptonigrin pathway.Tetrahedron Letters,1978,19(35):3207-3210.
[37]Gould S J,Chang C C.Streptonigrin biosynthesis.3.determination of the primary precursors to the 4-phenylpicolinic acid portion.Journal of The American Chemical Society,1980,102(5):1702-1706.
[38]Gould S J,Chang C C,Darling D S.Streptonigrinbiosynthesis.4.details of the tryptophan metabolism.Journal of The American Chemical Society,1980,102(5):1707-1712.
[39]Xu F,Kong D K,He X Y,et al.Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C Bond.Journal of The American Chemical Society,2013,135(5):1739-1748.
[40]Wu S F,Huang T T,Xie D,et al.Xantholipin B produced by the StnR inactivation mutant Streptomyces flocculus CGMCC 4.1223WJN-1.Journal of Antibiotics,2017,70(1):90-95.
[41]Wo J,Kong D K,Brock N L,et al.Transformation of streptonigrin to streptonigrone:flavin reductase-mediated flavin-catalyzed concomitant oxidative decarboxylation of picolinic acid derivatives.American Chemical Society Catalysis,2016,6(5):2831-2835.
[42]Kong D K,Zou Y,Zhang Z,et al.Identification of(2S,3S)-betamethyltryptophan as the real biosynthetic intermediate of antitumor agent streptonigrin.Scientific Reports,2016,6:20273.
[43]Kadela M,Jastrzebska M,Bebenek E,et al.Synthesis,structure and cytotoxic activity of mono-and dialkoxy derivatives of 5,8-quinolinedione.Molecules,2016,21(2):156.
[44]Sandelier M J,De Shong P.Reductive cyclization of onitrophenylpropargyl alcohols:facile synthesis of substituted quinolines.Organic Letters,2007,9(17):3209-3212.
[45]Zhang X,Xu X F,Yu L T,et al.Three-component reactions of aldehydes,amines,and alkynes/alkenes catalyzed by trifluoromethanesulfonic acid:an efficient route to substituted quinolines.Asian Journal of Organic Chemistry,2014,3(3):281-284.
[46]Borel C R,Barbosa L C A,Maltha C R A,et al.A facile one-pot synthesis of 2-(2-pyridyl)quinolines via Povarov reaction.Tetrahedron Letters,2015,56(5):662-665.
[47]Mc Elroy W T,De Shong P.Synthesis of the CD-ring of the anticancer agent streptonigrin:studies of aryl-aryl coupling methodologies.Tetrahedron,2006,62(29):6945-6954.
[48]Chan B K,Ciufolini M A.Total synthesis of streptonigrone.Journal of Organic Chemistry,2007,72(22):8489-8495.
[49]Cai W,Hassani M,Karki R,et al.Synthesis,metabolism and in vitro cytotoxicity studies on novel iavendamycin antitumor agents.Bioorganic&Medicinal Chemistry,2010,18(5):1899-1909.
[50]Mandewale M C,Thorat B,Patil U,et al.Developments in quinoline synthesis:a review.Heterocyclic Letters,2015,5(3):475-488.
[51]Burke P J,Toki B E,Meyer D W,et al.Novelimmunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl-amine linker system.Bioorganic&Medicinal Chemistry Letters,2009,19(10):2650-2653.
[52]Xia X,Lin S J,Xia X X,et al.Significance of agitation-induced shear stress on mycelium morphology and lavendamycin production by engineered Streptomyces flocculus.Applied Microbiology and Biotechnology,2014,98(10):4399-4407.
[2]Heikal A,Hards K,Cheung C Y,et al.Activation of type II NADHdehydrogenase by quinolinequinones mediates antitubercular cell death.Journal of Antimicrobial Chemotherapy,2016,71(10):2840-2847.
[3]Kadela-Tomanek M,Pawelczak B,Jastrzgbska M,et al.Structural,vibrational and quantum chemical investigations for 6,7dichloro-2-methyl-5,8-quinolinedione.Cytotoxic and molecular docking studies.Journal of Molecular Structure,2018,1168:73-83.
[4]Testoni M I,Bolzán A D,Bianchi M S,et al.Effects of antioxidants on streptonigrin-induced DNA damage and clastogenesis in CHOcells.Mutation Research,1997,373(2):201-206.
[5]Testoni M I,Bianchi N O,Bianchi M S.The kinetics of chromosome and DNA damage by streptonigrin in CHO cells.Mutation Research,1995,334(1):23-31.
[6]Andersson R C.Induction of sister-chromatid exchanges by streptonigrin,an antibiotic and antineoplastic agent.Hereditas,1981,95(1):141-148.
[7]DuFrain R J,Littlefield L G,Morrison W D,et al.Evaluation of chemically induced cytogenetic lesions in rabbit oocytes.III.Apost-implantation analysis of streptonigrin effects.Mutation Research,1984,127(1):73-79.
[8]Cadieux B,Colavecchio A,Jeukens J,et al.Prophage induction reduces shiga toxin producing Escherichia coli(STEC)and salmonella entericaon tomatoes and spinach:a model study.Food Control,2018,89:250-259.
[9]Cone R,Hasan S,Lown J.The mechanism of the degradation of DNA by streptonigrin.Canadian Journal of Biochemistry,1976,54(3):219-223.
[10]Rao K V,Cullen W P.Streptonigrin,an antitumor substance.I.Isolation and characterization.Antibiotics Annual,1959,2010(3):950-953.
[11]Brazhnikova M G,Ponomarenko V I,Kovsharova I N,et al.Study on bruneomycin produced by act.albus var.Bruneomycini and its identification with streptonigrin.Antibiot Khimioter,1968,13(2):99-102.
[12]Malkina N D,DudnikIu V,Lysenkova L N,et al.Induction of antibiotic formation by inactive cultures of actinomycetes.Amutant strain of Streptomyces helvaticus,a new producer of bruneomycin.Antibiot Khimioter,1995,40(6):3-6.
[13]Wang H S,Yeo S L,Xu J,et al.Isolation of streptonigrin and its novel derivative from Micromonospora as inducing agents of p53-dependent cell apoptosis.Journal of Natural Products,2002,65(5):721-724.
[14]Jin Y Y,Yoon T M,Kim W K,et al.Kitasatospora sp.MJM383strain producing two antitumor agents,streptonigrin and oxopropaline G.Journal of Microbiology and Biotechnology,2005,15(5):1140-1145.
[15]Sugiura Y,Kuwahara J,Suzuki T.DNA interaction and nucleotide sequence cleavage of copper-streptonigrin.Biochimicaet Biophysica Acta,1984,782(3):254-261.
[16]Anderberg P I,Harding M M.The effect of metal ions on the electrochemistry of the antitumor antibiotic streptonigrin.Journal of Inorganic Biochemistry,2004,98(5):720-726.
[17]Yamashita Y,Kawada S,Fujii N,et al.Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin.Cancer Research,1990,50(18):5841-5844.
[18]Gavriil M,Tsao C C,Mandiyan S,et al.Specific IKK beta inhibitor IV blocks streptonigrin-induced NF-kappa B activity and potentiates its cytotoxic effect on cancer cells.Molecular Carcinogenesis,2009,48(8):678-684.
[19]Beall H D,Murphy A M,Siegel D,et al.Nicotinamide adenine dinucleotide(phosphate):quinoneoxidoreductase(DT-diaphorase)as a target for bioreductive antitumor quinones:quinone cytotoxicity and selectivity in human lung and breast cancer cell lines.Molecular Pharmacology,1995,48(3):499-504.
[20]Cohen M M,Shaw M W,Craig A P.The effects of streptonigrin on cultured human leukocytes.Proceedings of the National Academy of Sciences,1963,50(50):16-24.
[21]Sanchez J,Bianchi M S,Ciancio V R,et al.Analysis of spontaneous and streptonigrin-induced sister chromatid exchanges in peripheral iymphocytes of aircrew members of international flights.Journal of Environmental Pathology Toxicology and Oncology,2008,27(4):277-285.
[22]Mencucci M V,Bravo M V,Bianchi M S,et al.Streptonigrin induces delayed chromosomal instability involving interstitial telomeric sequences in chinese hamster ovary cells.Mutation Research-Genetic Toxicology and Environmental Mutagenesis,2012,747(1):46-52.
[23]Dreyton C J,Anderson E D,Subramanian V,et al.Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation.Bioorganic&Medicinal Chemistry,2014,22(4):1362-1369.
[24]Park S,Chun S.Streptonigrin inhibits beta-Catenin/Tcf signaling and shows cytotoxicity in beta-catenin-activated cells.Biochimicaet Biophysica Acta,2011,1810(12):1340-1345.
[25]Khandoga N,Pohl U.Gap junction communications promote streptonigrin-induced apoptosis in He La cells.Journal of Vascular Research,2006,43(1):50.
[26]Ambaye N,Chen C H,Khanna S,et al.Streptonigrininhibits SENP1 and reduces the protein level of hypoxia-inducible factor 1alpha(HIF1 alpha)in cells.Biochemistry,2018,57(11):1807-1813.
[27]Lewis A M,Ough M,Du J,et al.Targeting NAD(P)H:quinoneoxidoreductase(nqo1)pancreatic cancer.Molecular Carcinogenesis,2017,56(7):215-224.
[28]Gavriil M,Tsao C C,Mandiyan S,et al.Specific IKK beta inhibitor IV blocks streptonigrin-induced NF-kappa B activity and potentiates its cytotoxic effect on cancer cells.Molecular Carcinogenesis,2009,48(8):678-684.
[29]Gutteridge J M.Streptonigrin-induced deoxyribosedegradation:inhibition by superoxide dismutase,hydroxylradical scavengers and ironchelators.Biochemical Pharmacology,1984,33(19):3059-3062.
[30]Krishna M C,Halevy R F,Zhang R,et al.Modulation of streptonigrincytotoxicitybynitroxide SOD mimics.Free Radical Biology&Medicine,1994,17(5):379-388.
[31]De Graff W,Hahn S M,Mitchell J B,et al.Free radical modes of cytotoxicity of adriamycinandstreptonigrin.Biochemical Pharmacology,1994,48(7):1427-1435.
[32]Kadela-Tomanek M,Jastrzebska M,Bebenek E,et al.Newacetylenic amine derivatives of 5,8-quinolinediones:synthesis,crystal structure and antiproliferative activity.Crystals,2017,7(1):15.
[33]Rao K V,Biemann K,Woodward R B.The structure of streptonigrin.Journal of The American Chemical Society.1963,85(16):2532-2533.
[34]Bringmann G,Reichert M,Hemberger Y.The absolute configuration of streptonigrin.Tetrahedron,2008,64(3):515-521.
[35]Gould S J,Chang C C.Streptonigrinbiosynthesis.1.origin of the 4-phenylpicolinic acid moiety.Journal of The American Chemical Society,1977,99(16):5496-5497.
[36]Gould S J,Darling D S.Streptonigrin biosynthesis.2.the isolation ofβ-methyltryptophanand its intermediacy in the streptonigrin pathway.Tetrahedron Letters,1978,19(35):3207-3210.
[37]Gould S J,Chang C C.Streptonigrin biosynthesis.3.determination of the primary precursors to the 4-phenylpicolinic acid portion.Journal of The American Chemical Society,1980,102(5):1702-1706.
[38]Gould S J,Chang C C,Darling D S.Streptonigrinbiosynthesis.4.details of the tryptophan metabolism.Journal of The American Chemical Society,1980,102(5):1707-1712.
[39]Xu F,Kong D K,He X Y,et al.Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C Bond.Journal of The American Chemical Society,2013,135(5):1739-1748.
[40]Wu S F,Huang T T,Xie D,et al.Xantholipin B produced by the StnR inactivation mutant Streptomyces flocculus CGMCC 4.1223WJN-1.Journal of Antibiotics,2017,70(1):90-95.
[41]Wo J,Kong D K,Brock N L,et al.Transformation of streptonigrin to streptonigrone:flavin reductase-mediated flavin-catalyzed concomitant oxidative decarboxylation of picolinic acid derivatives.American Chemical Society Catalysis,2016,6(5):2831-2835.
[42]Kong D K,Zou Y,Zhang Z,et al.Identification of(2S,3S)-betamethyltryptophan as the real biosynthetic intermediate of antitumor agent streptonigrin.Scientific Reports,2016,6:20273.
[43]Kadela M,Jastrzebska M,Bebenek E,et al.Synthesis,structure and cytotoxic activity of mono-and dialkoxy derivatives of 5,8-quinolinedione.Molecules,2016,21(2):156.
[44]Sandelier M J,De Shong P.Reductive cyclization of onitrophenylpropargyl alcohols:facile synthesis of substituted quinolines.Organic Letters,2007,9(17):3209-3212.
[45]Zhang X,Xu X F,Yu L T,et al.Three-component reactions of aldehydes,amines,and alkynes/alkenes catalyzed by trifluoromethanesulfonic acid:an efficient route to substituted quinolines.Asian Journal of Organic Chemistry,2014,3(3):281-284.
[46]Borel C R,Barbosa L C A,Maltha C R A,et al.A facile one-pot synthesis of 2-(2-pyridyl)quinolines via Povarov reaction.Tetrahedron Letters,2015,56(5):662-665.
[47]Mc Elroy W T,De Shong P.Synthesis of the CD-ring of the anticancer agent streptonigrin:studies of aryl-aryl coupling methodologies.Tetrahedron,2006,62(29):6945-6954.
[48]Chan B K,Ciufolini M A.Total synthesis of streptonigrone.Journal of Organic Chemistry,2007,72(22):8489-8495.
[49]Cai W,Hassani M,Karki R,et al.Synthesis,metabolism and in vitro cytotoxicity studies on novel iavendamycin antitumor agents.Bioorganic&Medicinal Chemistry,2010,18(5):1899-1909.
[50]Mandewale M C,Thorat B,Patil U,et al.Developments in quinoline synthesis:a review.Heterocyclic Letters,2015,5(3):475-488.
[51]Burke P J,Toki B E,Meyer D W,et al.Novelimmunoconjugates comprised of streptonigrin and 17-amino-geldanamycin attached via a dipeptide-p-aminobenzyl-amine linker system.Bioorganic&Medicinal Chemistry Letters,2009,19(10):2650-2653.
[52]Xia X,Lin S J,Xia X X,et al.Significance of agitation-induced shear stress on mycelium morphology and lavendamycin production by engineered Streptomyces flocculus.Applied Microbiology and Biotechnology,2014,98(10):4399-4407.