Daily administration of tubuloclustin (1 mg/kg, 5 d, i.p.) to BDF1 mice with i.p. transplanted P388 leukemia extended statistically significantly by 45% their life spans compared with those of untreated controls (17 vs. 11.7 ± 3 d). The possibility in principle of preparing 2-methoxyestradiol analogs with a linker bonded through a steroid C6 ester was demonstrated. However, the resulting conjugates IIa and IIb were unstable with respect to a strong tendency for elimination from the C6–C7 bond. This may have been the reason for their low cytotoxicity in the MTT assay on A549 cell culture (IC50 > 10 μM). It was concluded that conjugates of higher stability must be synthesized as potential antitumor agents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
The in vivo trials were conducted according to current RF methodical instructions for humanitarian handling of laboratory animals [9] and regulatory requirements of 1) the civilian RF code, RF Budget Code, FZ “On the contract system for purchasing products, works, or services for state and municipal needs” of Jul. 21, 2005, No. 94-FZ and other RF regulatory acts based on sect. 32, part 2, art. 55 of FZ No. 94-FZ; 2) GOST P53434-2009, “Principles of Laboratory Practices”; 3) FZ of Apr. 12, 2010, No. 61-FZ “On Circulation of Medicines” (art. 10, 11, 12, 13, 28, 29, 30, 38, 39, 40, 41); and 4) Russian Ministry of Health and Social Development Order of Aug. 23, 2010, No. 708n “On Approval of Laboratory Practice Rules”.
References
R. A. Stanton, K. M. Gernert, J. H. Nettles, and R. Aneja, Med. Res. Rev., 31(3), 443 – 481 (2011).
O. N. Zefirova, E. V. Nurieva, A. N. Ryzhov, et al., Zh. Org. Khim., 41(3), 329 – 362 (2005).
O. N. Zefirova, A. G. Diikov, N. V. Zyk, and N. S. Zefirov, Izv. Ross. Akad. Nauk, Ser. Khim., 56(4), 655 – 662 (2007).
O. N. Zefirova, E. V. Nurieva, H. Lemcke, et al., Mendeleev Commun., 18(4), 183 – 185 (2008).
O. N. Zefirova, E. V. Nurieva, H. Lemcke, et al., Bioorg. Med. Chem. Lett., 18(18), 5091 – 5094 (2008).
J. Chen, T. Liu, X. Dong, and Y. Hu, Mini-Rev. Med. Chem., 9(10), 1174 – 1190 (2009).
O. N. Zefirova, E. V. Nurieva, D. V. Shishov, et al., Bioorg. Med. Chem., 19(18), 5529 – 5538 (2011).
O. N. Zefirova, H. Lemcke, M. Lantow, et al., ChemBioChem, 14(12), 1444 – 1449 (2013).
E. M. Treshchalina, N. V. Andronova, G. K. Gerasimova, et al., in: Handbook for Preclinical Drug Trials. Part One [in Russian], Izd. Grif i K., Moscow (2012), 39, pp. 642 – 657.
M. Rosner, H.-G. Capraro, A. E. Jacobson, et al., J. Med. Chem., 24(3), 257 – 261 (1981).
P. Kerekes, P. N. Sharma, A. Brossi, et al., J. Med. Chem., 28(9), 1204 – 1208 (1985).
N. F. Magri and D. G. I. Kingston, J. Nat. Prod., 51(2), 298 – 306 (1988).
Z. Fang, G. E. Agoston, G. Ladouceur, et al., Tetrahedron, 65(1), 10535 – 10543 (2009).
T. Mosmann, J. Immunol. Methods, 65(1 – 2), 55 – 63 (1983).
Acknowledgments
The work was supported financially by grants of the RFBR (12-03-00720, 13-03-12460) and the German Academic Exchange Service (DAAD) under the auspices of a collaborative agreement between Moscow and Rostock Universities.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 48, No. 6, pp. 19 – 24, June, 2014.
Rights and permissions
About this article
Cite this article
Zefirova, O.N., Nurieva, E.V., Glazkova, Y.S. et al. Antiproliferative Activity of Tubuloclustin and its Steroid Analogs. Pharm Chem J 48, 373–378 (2014). https://doi.org/10.1007/s11094-014-1113-8
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-014-1113-8