Search for antitumor activity among derivatives of the 2,5-dihydropyrrole-2,5-dione

Authors

  • S. S. Tarnavskiy Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • G. G. Dubinina Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • S. M. Golovach Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author
  • S. M. Yarmoluk Institute of Molecular Biology and Genetics, NAS of Ukraine 150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 Author

DOI:

https://doi.org/10.7124/bc.00065E

Abstract

39 derivatives of the 2,5-dihydropyrrole-2,5-dione were synthesized and tested on antitumor activity. The l-benzyl-3-chloro-4-(3-hydro-xyanilino)-2,5-dihydro-IH-2,5-pyrroledione (5.2) was selected after pre-screening and tested on 56 cell lines of human tumors. The compound 5.2 exhibits antitumor activity: CI50 2.68μM, LC50 31.7 μM (cell line MDA-MB-435 (Breast Cancer)); GI50 3.35 μM, LC50 37.6 μM (cell line OVCAR-3 (Ovarian Cancer)); GI50 6.75 μM, LC50 44.5 μM (cell line NCI-H23 (Non-small Cell Lung Cancer)).

References

Omura S, Iwai Y, Hirano A, Nakagawa A, Awaya J, Tsuchya H, Takahashi Y, Masuma R. A new alkaloid AM-2282 OF Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization. J Antibiot (Tokyo). 1977;30(4):275-82.

Furusaki A, Hashiba N, Matsumoto T, Hirano A, Iwai Y, Omura S. X-Ray crystal structure of staurosporine: a new alkaloid from a Streptomyces strain. J Chem Soc, Chem Commun. 1978;(18):800.

Furusaki A, Hashiba N, Matsumoto T, Hirano A, Iwai Y, Omura S. The crystal and molecular structure of staurosporine, a new alkaloid from a Streptomyces strain. Bull Chem Soc Jpn. 1982;55(12):3681–5.

Fischer PM, Lane DP. Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem. 2000;7(12):1213-45.

Senderowicz AM. The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01. Oncologist. 2002;7 Suppl 3:12-9.

Bailly C, Qu X, Chaires JB, Colson P, Houssier C, Ohkubo M, Nishimura S, Yoshinari T. Substitution at the F-ring N-imide of the indolocarbazole antitumor drug NB-506 increases the cytotoxicity, DNA binding, and topoisomerase I inhibition activities. J Med Chem. 1999;42(15):2927-35.

Andricopulo AD, Yunes RA, Nunes RJ, Savi AOS, Correa R, Cruz AB, Filho VC. Synthesis and antibacterial activity of cyclic imides: 3,4-dichloromaleimides and 4-substituted 3-chloromaleimides. Quim Nova. 1998; 21(5):573-7.

Dubinina GG, Tarnavskyy SS, Golovach SM, Yarmoluk SM. Interaction of 3,4-dichloro maleimide along with N- and S- nucleophiles. Ukr Khim Zh. 2002; 68(8):47-51.

Yarmoluk SM, Dubinina GG, Volovenko YM, Shishkina SV, Shishkin OV. Reaction of N-Substituted 3,4-Dichloromaleimides with a-Mercaptoazaheterocycles. Heterocycles. 2001;55(11):2189-98.

Published

2003-05-20

Issue

Section

Bioorganic Chemistry