目的综述氮芥类化合物在抗肿瘤方面的研究进展。方法依据近年国内外文献阐述脂肪氮芥、芳基氮芥、芳烷基氮芥、大环类氮芥、磷酰胺氮芥和金属配合物氮芥等的抗肿瘤活性,并且简述了氮芥的抗肿瘤机制。结果与结论氮芥类化合物在治疗肿瘤方面发挥了重要作用,是目前研究开发的热点领域之一,随着研究的不断深入,将有越来越多的高效、低毒的氮芥类抗肿瘤药物用于临床。
关键词
氮芥 /
抗肿瘤 /
抗癌 /
环磷酰胺 /
大环 /
金属配合物
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] YU K G,ZHOU C H,LI D H. Recent progress of the porphyrin-based anticancer drugs[J] . Chem Res Appl(化学研究与应用),2007,19(12):1296-1303.
[2] BARTZATT R,DONIGAN L. Two identical twin nitrogen mustard agents that express rapid alkylation activity at physiological pH 7.4 and 37 ℃[J] . Lett Drug Des Discov,2004,1:78-83.
[3] COGGIOLA B,PAGLIAI F,ALLEGRONE G,et al. Synthesis and biological activity of mustard derivatives of combretastatins[J] . Bioorg Med Chem Lett,2005,15(15):3551-3554.
[4] RACHID Z,BRAHIMI F,QIU Q Y,et al. Novel nitrogen mustard-armed combi-molecules for the selective targeting of epidermal growth factor receptor overexperessing solid tumors: discovery of an unusual structure-activity relationship[J] . J Med Chem,2007,50(11):2605-2608.
[5] URBANIAK M D,BINGHAM J P,HARTLEY J A,et al. Design and synthesis of a nitrogen mustard derivative stabilized by apo-neocarzinostatin[J] . J Med Chem,2004,47(19):4710-4715.
[6] HUANG Z H,LIN Z L,HUANG J L. A novel kind of antitumour drugs using sulfonamide as parent compound[J] . Eur J Med Chem,2001,36(11-12):863-872.
[7] GIRAUD I,RAPP M,MAURIZIS J C,et al. Synthesis and in vitro evaluation of quaternary ammonium derivatives of chlorambucil and melphalan,anticancer drugs designed for the chemotherapy of chondrosarcoma[J] . J Med Chem,2002,45(10):2116-2119.
[8] VIJAYARAGHAVAN S,JING B,VRABLIK T,et al. Enhanced hydrolytic stability and water solubility of an aromatic nitrogen mustard by conjugation with molecular umbrellas[J] . Bioconjugate Chem,2003,14(3):667-671.
[9] LUO W,ZHAO Y M,WANG Y X,et al. Synthesis and antitumor activity of benzoic nitrogen mustard derivatives[J] . Acta Pharm Sin(药学学报),2007,42(12):1327-1329.
[10] SUN Z Y,BOTROS E,SU A D,et al. Sulfoxide-containing aromatic nitrogen mustards as hypoxia-directed bioreductive cytotoxins[J] . J Med Chem,2000,43(22):4160-4168.
[11] KATSOULAS A,RACHID Z,BRAHIMI F,et al. Cytokinetics and mechanism of action of AKO4: a novel nitrogen mustard targeted to bcr-abl[J] . Leukemia Res,2005,29(5):565-572.
[12] HELSBY N A,WHEELER S J,PRUIJN F B,et al. Effect of nitroreduction on the alkylating reactivity and cytotoxicity of the 2,4-dinitrobenzamide-5-aziridine CB 1954 and the corresponding nitrogen mustard SN23862: distinct mechanisms of bioreductive activation [J] . Chem Res Toxicol,2003,16(4):469-478.
[13] MARKOWSKA A,RZANSKI A,WOLCZYNSKI S,et al. Synthesis and biological activity of carbocyclic lexitropsins with a bioreductive fragment[J] . Il Farmaco,2002,57(12):1019-1023.
[14] DUVAZ I N,SCANLON I,DUVAZ D N,et al. Significant differences in biological parameters between prodrugs cleavable by carboxypeptidase G2 that generate 3,5-difluoro-phenol and -aniline nitrogen mustards in gene-directed enzyme prodrug therapy systems[J] . J Med Chem,2004,47(10):2651-2658.
[15] KOUTSOUREA A I,FOUSTERIS M A,ARSENOU E S,et al. Rational design,synthesis,and in vivo evaluation of antileukemic activity of six new alkylating steroidal esters[J] . Bioorg Med Chem,2008,16(9):5207-5215.
[16] BARALDI P G,NUNEZ M D C,ESPINOSA A,et al. Distamycin A as stem of DNA minor groove alkylating agents[J] . Curr Top Med Chem,2004,4(2):231-239.
[17] COZZI P. A new class of cytotoxic DNA minor groove binders: α-halogenoacrylic derivatives of pyrrolecarbamoyl oligomers[J] . Il Farmaco,2001,56(1):57-65.
[18] WANG Y Q,WRIGHT S C,LARRICK J W. Synthesis and preliminary cytotoxicity of nitrogen mustard derivatives of distamycin A[J] . Bioorg Med Chem Lett,2003,13(3):459-461.
[19] BARALDI P G,NUNEZ M D C,ESPINOSA A,et al. Distamycin A as stem of DNA minor groove alkylating agents [J] . Curr Top Med Chem,2004,4(2):231-239.
[20] BARALDI P G,BERIA I,COZZI P,et al. Cinnamoyl nitrogen mustard derivatives of pyrazole analogues of tallimustine modified at the amidino moiety: design,synthesis,molecular modeling and antitumor activity studies[J] . Bioorg Med Chem,2004,12(14):3911-3921.
[21] BARALDI P G,COZZI P,GERONI C,et al. Novel benzoyl nitrogen mustard derivatives of pyrazole analogues of distamycin A: synthesis and antileukemic activity[J] . Bioorg Med Chem,1999,7(2):251-262.
[22] BARALDI P G,ROMAGNOLI R,BIANCHIB N,et al. Benzoyl nitrogen mustard derivatives of benzoheterocyclic analogues of netropsin: synthesis and biological activity[J] . Bioorg Med Chem,2003,11:2381-2388.
[23] YU K G,ZHOU C H,LI D H. Advances of macrocyclic compounds in pharmaceutical sciences[J] . Chin Pharm J(中国药学杂志),2008,43(7):1-9.
[24] GUO C C,TONG R B,LI K L. Chloroalkyl piperazine and nitrogen mustard porphyrins: synthesis and anticancer activity[J] . Bioorg Med Chem,2004,12(9):2469-2475.
[25] PARKER L L,ANDERSON F M,HARE C C,et al. Synthesis of novel DNA cross-linking antitumour agents based on polyazamacrocycles[J] . Bioorg Med Chem,2005,13(7):2389-2395.
[26] CHEN R Y,CHI G C,CHEN X R. Synthesis of 5′-O-(N,N-Bis(2-chloroethyl)phosphoramido) -2′,3′-O- isopropylidenenucleosides[J] . Chem J Chin Univ(高等学校化学学报),1996,17(3):429-431.
[27] LI C Z,WU J G,WANG L F,et al. Synthesis,characterization and antitumor activity of copper (Ⅱ) complex with nicotinamido-4-bis(2-chloroethyl) aminobenzaldimine[J] . J Inorg Biochem,1999,73(4):195-202.
[28] PARKER L L,LACY S M,FARRUGIA L J,et al. A novel design strategy for stable metal complexes of nitrogen mustards as bioreductive prodrugs[J] . J Med Chem,2004,47(23):5683 -5689.
[29] HUANG G H,ZHU X L,ZHANG N,et al. Preparation of lomustine thermo-sensitive liposomes and investigation of anti-tumor activity in vitro[J] . Chin Pharm J(中国药学杂志),2007,42(12):914-918.
[30] LUO Y,ZHUANG Y Y,ZHOU C H. Synthesis and anticancer activity of nitrogen mustard derivative[J] . Chin J Org Chem(有机化学),2007,27(suppl) :515.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
重庆市自然科学基金(CSTC,2007BB5369);西南大学基金(XSGX0602,SWUB2006018,SWUF2007023)
{{custom_fund}}