Synthesis and cytotoxicity of new 4-aza-2,3-didehydropodophyllotoxins
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DOI:
https://doi.org/10.15625/2525-2518/15577Keywords:
quinolin, podophyllotoxin, one-pot, cytotoxiccityAbstract
Five new 4-aza-2,3-didehydropodophyllotoxins were synthesized by a straightforward multi-component reaction in the hope of finding new structures with interesting anticancer activity. The “one-pot” synthesis process is developed to increase performance as well as minimize the steps involved. The obtained compounds with podophyllotoxin frame have the corresponding yields of 60-83%. Five new 4-aza-2,3-didehydropodophyllotoxins demonstrated comparable cytotoxicity against the Hep-G2, MCF7cell lines with an IC50 value of 52.2 - 261.2 µM with ellipsitine as the positive control.
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Wratten S. J., Wolfe M. S., Andersen R. J., and Faulkner D. J. - Antibiotic Metabolites from a Marine Pseudomonad, Antimicrob. Agents Chemother. 11 (3) (1977) 411-414. DOI: https://doi.org/10.1128/AAC.11.3.411
Berger J. M. and Wang J. C. - Recent developments in DNA topoisomerase II structure and mechanism, Curr. Opin. Struct. Biol. 6 (1) (1996) 84-90. DOI: https://doi.org/10.1016/S0959-440X(96)80099-6
Sakurai H., Miki T., Imakura Y., Shibuya M. - Metal- and photo-induced cleavage of DNA by podophyllotoxin, etoposide, and their related compounds, Mol. Pharmacol. 40 (6) (1991) 965-973.
Huang T. S., Shu C. H., Shih Y. L., Huang H. C. - Protein tyrosine phosphatase activities are involved in apoptotic cancer cell death induced by GL-331, a new homolog of etoposide, Cancer Lett. 110 (1996) 77-85. DOI: https://doi.org/10.1016/S0304-3835(96)04464-3
Huang T. S., Shu C. H., Yang W. K., Whang-Peng J. - Activation of CDC 25 phosphatase and CDC2 kinase involved in GL-331- induced apoptosis, Cancer Res. 57 (14) (1997) 2974-2978.
Cho S. J., Kashiwada Y., Bastow K. F. - Antitumor agents 164. Podophenazine, 2″ ,3″ - dichloropodophenazine, ben-zopodophenazine, and their 4β-p-nitroaniline derivatives as novel DNA topoisomerase II inhibitors, J. Med. Chem. 39 (7) (1996) 1396-1402. DOI: https://doi.org/10.1021/jm950548u
Wang Z. Q., Kuo Y. H., Schnur D., Bowen J. P. - Antitumor agents 113. New 4β-arylamino derivatives of 4′-O-demethylepipodo-phyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II, J. Med. Chem. 33 (9) (1990) 2660-2666. DOI: https://doi.org/10.1021/jm00171a050
Zhou X. M., Wang Z. Q., Chang J. Y., Chen H. X. - Antitumor agents 120. New 4-substituted benzylamine and benzyl ether derivatives of 4′ -O-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II, J. Med. Chem. 34 (12) (1991) 3346-3350. DOI: https://doi.org/10.1021/jm00116a001
Lee K. H., Beers S. A., Mori M., Wang Z. Q. - Antitumor agents 111. New 4-hydroxylated and 4-halogenated anilino derivatives of 4-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II, J. Med. Chem. 33 (5) (1990) 1364-1368. DOI: https://doi.org/10.1021/jm00167a013
Chang J. Y., Han F. S., Liu S. Y., Wang Z. Q., Lee K. H. - Effect of 4β-arylamino derivatives of 4′ -O-demethylpodophyllotoxin on human DNA topoisomerase II, tubulin polymerization, KB cells, and their resistant variants, Cancer Res. 51 (1991) 1755-1759.
Terada T., Fujimoto K., Nomura M. - Antitumor agents 3. Synthesis and biological activity of 4β-alkyl derivatives con-taining hydroxyl, amino, and amido groups of 4′-O-demethyl-4-deoxypodophyllotoxin as antitumor agents, J. Med. Chem. 36 (12) (1993) 1689-1699. DOI: https://doi.org/10.1021/jm00064a002
Zhou X. M., Lee K. J. H., Cheng J., Wu S. S. - Antitumor agents 144. New γ -lactone ring-modified arylamino etoposide analogs as inhibitors of human DNA topoisomerase II, J. Med. Chem. 37 (2) (1994) 287-292. DOI: https://doi.org/10.1021/jm00028a012
Tomioka K., Kubota Y., and Koga K. - Synthesis and antitumor activity of podophyllotoxin aza-analogues, Tetra. Lett. 30 (22) (1989) 2953-2954. DOI: https://doi.org/10.1016/S0040-4039(00)99167-6
Roulland E., Bertounesque E., Huel C., Monneret C. - Synthesis of picropodophyllotoxin homolactone, Tetra. Lett. 41 (35) (2000) 6769-6773. DOI: https://doi.org/10.1016/S0040-4039(00)01136-9
Van Vliet D. S., Tachibana Y., Bastow K. F. - Antitumor agents: 207. Design, synthesis, and biological testing of 4β−anilino-2-fluoro-4′-demethylpodophyllotoxin analogues as cytotoxic and antiviral agents, J. Med. Chem. 44 (9) (2001) 1422-1428. DOI: https://doi.org/10.1021/jm000377f
Saulnier M. G., Langley D. R., Kadow J. F., Senter P. D. - Synthesis of etoposide phosphate, BMY-40481: a water-soluble clinically active prodrug of etoposide, Bioorg. Med. Chem. Lett. 4 (21) (1994) 2567-2572. DOI: https://doi.org/10.1016/S0960-894X(01)80285-7
Hu H., Liu S. Y., Cheng Y. C., Lee K. H. - Antitumor agents 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2′-chloro derivatives of etoposide and 4β-(arylamino)-4′-O-demethylpodophyllotoxins, J. Med. Chem. 35 (5) (1992) 866-871. DOI: https://doi.org/10.1021/jm00083a009
Cho S. J., Tropsha A., Suffness M. - Antitumor agents 163. Three-dimensional quantitative structure-activity relationship study of 4′-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q2-GRS approach, J. Med. Chem. 39 (7) (1996) 1383-1395. DOI: https://doi.org/10.1021/jm9503052
Kamal A., Suresh P., Mallareddy A., Kumar B. A., Reddy P. V., Raju P., Tamboli J. R., Shaik T. B., Jain N., Kalivendi S. V. - Synthesis of a new 4-aza-2, 3-didehydropodophyllotoxin analogues as potent cytotoxic and antimitotic agents, Bioorganic and Medicinal Chemistry 19 (2011) 2349-2358. DOI: https://doi.org/10.1016/j.bmc.2011.02.020
Botes M. G., Pelly S. C., Blackie M. A. L. -. Synthesis of 4-Azapodophyllotoxins with Anticancer Activity by Multicomponent Reactions (Review), Chem Heterocycl Comp 50 (2014) 119-138. DOI: https://doi.org/10.1007/s10593-014-1455-x
Shi F., Zeng X. N., Tu S. J. - Facile synthesis of new 4-aza-podophyllotoxin analogs via microwave-assisted multi-component reactions and evaluation of their cytotoxic activity, Bioorg. Med. Chem. Lett. 21 (2011) 7119-7123. DOI: https://doi.org/10.1016/j.bmcl.2011.09.082
Semenova M. N., Kiselyov A. S., Semenov V. V. - Polyalkoxybenzenes from Plants. 5. Parsley Seed Extract in Synthesis of Azapodophyllotoxins Featuring Strong Tubulin Destabilizing Activity in the Sea Urchin Embryo and Cell Culture Assays, J. Med. Chem. 54 (2011) 7138-7149. DOI: https://doi.org/10.1021/jm200737s
Kumar A., Kumar V., Alegria A. E., Malhotra S. V. - N-Hydroxyethyl-4-aza-didehydropodophyllotoxin derivatives as potential antitumor agents, Eur. J. Pharm. Sci. 44 (2011) 21-26. DOI: https://doi.org/10.1016/j.ejps.2011.04.013
Kamal A., Reddy T. S., Polepalli S., Paidakula S., Srinivasulu V., Reddy V. G., Jain N., Shankaraiah N. - Synthesis and biological evaluation of 4-aza-2, 3-dihydropyridophenanthrolines as tubulin polymerization inhibitors, Bioorg. Med. Chem. Lett. 24 (2014) 3356-3360. DOI: https://doi.org/10.1016/j.bmcl.2014.05.096
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