Azinomycin B

Azinomycin B
Names
	IUPAC name (1S)-2-{[(1E)-1-[(3R,4R,5S)-3-Acetoxy-4-hydroxy-1-azabicyclo[3.1.0]hex-2-ylidene]-2-{[(1Z)-1-hydroxy-3-oxo-1-buten-2-yl]amino}-2-oxoethyl]amino}-1-[(2S)-2-methyl-2-oxiranyl]-2-oxoethyl 3-methoxy-5-methyl-1-naphthoate
	Other names Carzinophilin A; Carzinophillin A
Identifiers
CAS Number	106486-76-4;
3D model (JSmol)	Interactive image;
Beilstein Reference	9537192
ChEBI	CHEBI:50862;
ChemSpider	10270414;
PubChem CID	14476972;
UNII	051R55X44C;
	InChI InChI=1S/C31H33N3O11/c1-14-7-6-8-18-19(14)9-17(42-5)10-20(18)30(41)45-27(31(4)13-43-31)29(40)33-23(28(39)32-21(12-35)15(2)36)24-26(44-16(3)37)25(38)22-11-34(22)24/h6-10,12,22,25-27,35,38H,11,13H2,1-5H3,(H,32,39)(H,33,40)/b21-12-,24-23+/t22-,25+,26+,27+,31-,34?/m0/s1 Key: QIKVYJOCQXXRSJ-PKDLRSQSSA-N;
	SMILES Cc1cccc2c1cc(cc2C(=O)O[C@H](C(=O)N/C(=C/3\[C@H]([C@@H]([C@H]4N3C4)O)OC(=O)C)/C(=O)N/C(=C\O)/C(=O)C)[C@@]5(CO5)C)OC;
Properties
Chemical formula	C31H33N3O11
Molar mass	623.615 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Azinomycin B is a natural product that contains densely assembled functionalities with potent antitumor activity.^[1] It is isolated from Streptomyces sahachiroi^[2] which is reisolated from S. griseofuscus along with its analog azinomycin A.^[3] Azinomycin B can bind within the major groove of DNA and forms covalent interstrand crosslinks (ISCs) with the purine bases.^[4]^[5]^[6]^[7] The DNA alkylation and crosslinking by azinomycin B suggests its potent antitumor activity.^[8]

Biosynthesis

The biosynthesis of azinomycin B includes a type 1 polyketide synthase and several nonribosomal peptide synthetases.^[9]

Azinomycin B biosynthesis

References

^ Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.
^ Hata, T., Koga, F., Sano, Y., Kanamori, K., Matsumae, A., Sunagawa, R., Hoshi, T., Shima, T., Ito, S., and Tomizawa, S. (1954). Carzinophilin, a new tumor inhibitory substance produced by Streptomyces. I. J. Antibiot. 7A, 107–112.
^ Yokoi, K., Nagaoka, K., and Nakashima, T. (1986). Azinomycins A and B, new antitumor antibiotics. II. Chemical structures. Chem. Pharm. Bull. (Tokyo) 34, 4554–4561.
^ Armstrong, R.W., Salvati, M.E., and Nguyen, M. (1992). Novel interstrand cross-links induced by the antitumor antibiotic carzinophillin/azinomycin B. J. Am. Chem. Soc. 114, 3144–3145.
^ Hartley, J.A., Hazrati, A., Kelland, L.R., Khanim, R., Shipman, M., Suzenet, F., and Walker, L.F. (2000). A synthetic azinomycin analogue with demonstrated DNA cross-linking activity: Insights into the mechanism of action of this class of antitumor agent. Angew. Chem. Int. Ed. Engl. 39, 3467–3470.
^ Coleman, R.S., Perez, R.J., Burk, C.H., and Navarro, A. (2002). Studies on the mechanism of action of azinomycin B: definition of regioselectivity and sequence selectivity of DNA cross-link formation and clarification of the role of the naphthoate. J. Am. Chem. Soc. 124, 13008–13017.
^ LePla, R.C., Landreau, C.A.S., Shipman, M., and Jones, G.D. (2005). On the origin of the DNA sequence selectivity of the azinomycins. Org. Biomol. Chem. 3, 1174–1175.
^ Kelly, G.T., Liu, C., Smith, R., III, Coleman, R.S., and Watanabe, C.M.H. (2006). Cellular effects induced by the antitumor agent azinomycin B. Chem. Biol. 13, 485–492.
^ Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.

[1] Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.

[2] Hata, T., Koga, F., Sano, Y., Kanamori, K., Matsumae, A., Sunagawa, R., Hoshi, T., Shima, T., Ito, S., and Tomizawa, S. (1954). Carzinophilin, a new tumor inhibitory substance produced by Streptomyces. I. J. Antibiot. 7A, 107–112.

[3] Yokoi, K., Nagaoka, K., and Nakashima, T. (1986). Azinomycins A and B, new antitumor antibiotics. II. Chemical structures. Chem. Pharm. Bull. (Tokyo) 34, 4554–4561.

[4] Armstrong, R.W., Salvati, M.E., and Nguyen, M. (1992). Novel interstrand cross-links induced by the antitumor antibiotic carzinophillin/azinomycin B. J. Am. Chem. Soc. 114, 3144–3145.

[5] Hartley, J.A., Hazrati, A., Kelland, L.R., Khanim, R., Shipman, M., Suzenet, F., and Walker, L.F. (2000). A synthetic azinomycin analogue with demonstrated DNA cross-linking activity: Insights into the mechanism of action of this class of antitumor agent. Angew. Chem. Int. Ed. Engl. 39, 3467–3470.

[6] Coleman, R.S., Perez, R.J., Burk, C.H., and Navarro, A. (2002). Studies on the mechanism of action of azinomycin B: definition of regioselectivity and sequence selectivity of DNA cross-link formation and clarification of the role of the naphthoate. J. Am. Chem. Soc. 124, 13008–13017.

[7] LePla, R.C., Landreau, C.A.S., Shipman, M., and Jones, G.D. (2005). On the origin of the DNA sequence selectivity of the azinomycins. Org. Biomol. Chem. 3, 1174–1175.

[8] Kelly, G.T., Liu, C., Smith, R., III, Coleman, R.S., and Watanabe, C.M.H. (2006). Cellular effects induced by the antitumor agent azinomycin B. Chem. Biol. 13, 485–492.

[9] Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.

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