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Kovalenko SI, Nosulenko IS, Voskoboynik AY, et al. Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity. Sci Pharm. 2012;80(4):837-65doi: 10.3797/scipharm.1208-07.
Kovalenko, S. I., Nosulenko, I. S., Voskoboynik, A. Y., Berest, G. G., Antypenko, L. N., Antypenko, A. N., & Katsev, A. M. (2012). Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity. Scientia pharmaceutica, 80(4), 837-65. https://doi.org/10.3797/scipharm.1208-07
Kovalenko, Sergey I, et al. "Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity." Scientia pharmaceutica vol. 80,4 (2012): 837-65. doi: https://doi.org/10.3797/scipharm.1208-07
Kovalenko SI, Nosulenko IS, Voskoboynik AY, Berest GG, Antypenko LN, Antypenko AN, Katsev AM. Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity. Sci Pharm. 2012 Oct-Dec;80(4):837-65. doi: 10.3797/scipharm.1208-07. Epub 2012 Oct 04. PMID: 23264935; PMCID: PMC3528059.
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Sci Pharm. 2012 Oct-Dec;80(4):837-65. doi: 10.3797/scipharm.1208-07. Epub 2012 Oct 04.

Substituted 2-[(2-Oxo-2H-[1,2,4]triazino [2,3-c]quinazolin-6-yl)thio]acetamides with Thiazole and Thiadiazole Fragments: Synthesis, Physicochemical Properties, Cytotoxicity, and Anticancer Activity.

Scientia pharmaceutica

Sergey I Kovalenko, Inna S Nosulenko, Alexey Yu Voskoboynik, Galina G Berest, Lyudmyla N Antypenko, Alexey N Antypenko, Andrey M Katsev

Affiliations

  1. Zaporozhye State Medical University, 69035, Zaporozhye, Ukraine.

PMID: 23264935 PMCID: PMC3528059 DOI: 10.3797/scipharm.1208-07

Abstract

The series of novel N-R-2-[(3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]acetamides with thiazole and thiadiazole fragments in a molecule were obtained by alkylation of potassium salts 1.1-1.4 by N-hetaryl-2-chloroacetamides and by aminolysis of activated acids 2.1-2.4 with N,N'-carbonyldiimidazole (CDI). The structures of compounds were determined by IR, (1)H NMR, MS, and EI-MS analysis. The results of cytotoxicity evaluated by the bioluminescence inhibition of bacterium Photobacterium leiognathi, Sh1 showed that the compounds have considerable cytotoxicity. The synthesized compounds were tested for anticancer activity in NCI against 60 cell lines. Among the highly active compounds 3.1, 3.2, and 6.5, 2-[(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)thio]-N-(1,3-thiazol-2-yl)acetamide (3.1) was found to be the most active anticancer agent against the cell lines of colon cancer (GI(50) at 0.41-0.69 μM), melanoma (GI(50) 0.48-13.50 μM), and ovarian cancer (GI(50) 0.25-5.01 μM). The structure-activity relationship (SAR-analysis) was discussed.

Keywords: Anticancer; Bioluminescence inhibition; SAR; Thiadiazoles; Thiazoles; [1,2,4]Triazino[2,3-c]quinazolines

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