New O-alkylaminoethylated derivatives of 3-hydroximinocholestene were synthesised and studied for in vitro cytotoxic effects. The obtained oily oxime ethers were solidified by preparing their oxalate salts. The steroidal compounds were screened against 60 human cancer cell lines at 10 μM. The study indicated that the compounds display selective cytotoxicity against leukemia cell lines. Dimethylamine (7a) and pyrrolidine (7d) derived O-alkylated steroidal oxalates displayed percent growth inhibition of 73.36%and 69.97 %, respectively, against CCRF-CEM leukemia cancer cell line. Partition coefficient values of the new steroids were also estimated to study the correlation of lipophilicity with the biological activity. The overall percentage growth inhibition of leukemia cell lines was 42% and 41% when treated with compounds 7a and 7d, respectively. Results obtained in the present study would help developing potent cytotoxic compounds with specificity toward leukemia cancer.
Similar content being viewed by others
References
A. Jemal, R. Siegel, E. Ward, et al., CA Cancer J. Clin., 68(1), 7 – 30 (2018).
P. Hemant and S. Gupta, IJARPB, 1(1), 10 – 18 (2011).
K. Alhanout, J. M. Rolain, and J. M. Brunel, Curr. Med. Chem., 17(32), 3909 – 3917 (2010).
B. V. Zaane, E. Nur, A. Squizzato, et al., J. Thromb. Haemost., 8(11), 2483 – 2493 (2010).
S. K. Lafont, Eur. J. Entomol., 92(1), 355 – 377 (2013).
S. Koduru, F. O. Jimoh, D. S. Grierson, and A. J. Afolayan, J. Pharmacol. Toxicol., 2(2), 160 – 167 (2007).
G. M. Allan, H. R. Lawrence, J. Cornet, et al., J. Med. Chem., 49(4), 1325 – 1345 (2006).
P. C. Acharya and R. Bansal, Arch. Pharm., 347(3), 193 – 199 (2014).
J. G. Cui, L. Fan, L. L. Huang, et al., Steroids, 74(1), 62 – 72 (2009).
J. G. Cui, L. Fan, L. L. Huang, et al., Steroids, 74(12), 989 – 995 (2009).
J. Rodríguez, L. Nuñez, S. Peixinho, and C. Jiménez, Tetrahedron Lett., 38(10), 1833 – 1836 (1997).
N. Deive, J. Rodríguez, and C. Jiménez, J. Med. Chem., 44(16), 2612 – 2618 (2001).
J. Poza, M. Rega, V. Paz, et al., Bioorg. Med. Chem., 15(14), 4722 – 4740 (2007).
Y. Huang, J. Cui, S. Chen, et al., Mar. Drugs, 12(4), 1715 – 1731 (2014).
V. Richmond, V. P. Careaga, P. Sacca, et al., Steroids, 84, 7 – 10 (2014).
D. P. Jindal, R. Chattopadhaya, S. Guleria, and R. Gupta, Eur. J. Med. Chem., 38(11 – 12), 1025 – 1034 (2003).
W. H. Chen, X. B. Shao, R. Moellering, et al., Bioconjug. Chem., 17(6), 1582 – 1591 (2006).
OECD Test No. 107, Partition Coefficient (n-octanol / water): Shake Flask Method, OECD Publishing (1995).
R. H. Shoemaker, Nat. Rev. Cancer, 6(10), 813 – 823 (2006).
V. Vanicha and K. Kirtikara, Nat. Protoc., 1(3), 1112 – 1116 (2006).
A. A. Wakharde, A. H. Awad, A. Bhagat, and S. M. Karuppayil, Am. J. Clin. Microbiol. Antimicrob., 1(2), Article no. 1009 (2018).
Acknowledgements
The authors express appreciation to the National Cancer Institute (United States) for in vitro antineoplastic activity assay. The authors are also thankful to the University Grants Commission (New Delhi, India) for providing financial support (F.4-1/2006(BSR)/5-94/2007) to carrying out this research work.
Conflict of Interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Suryan, A., Bansal, R. Synthesis and In Vitro Studies of O-Alkylaminoethylated Derivatives of 3E-Hydroximinocholestene as Potent and Selective Antileukemic Agents. Pharm Chem J 54, 918–923 (2020). https://doi.org/10.1007/s11094-020-02297-6
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-020-02297-6