Published November 27, 2024 | Version v1
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Syntheses and evaluation of novel 3-hydroxy-1,3-diaryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides as potential anticancer agents

Authors/Creators

  • 1. Institute of Molecular Biology and Genetics of National Academy of Sciences Ukraine, Kyiv, Ukraine
  • 2. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine|Nizhyn Mykola Gogol State University, Nizhyn, Ukraine
  • 3. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • 4. Nizhyn Mykola Gogol State University, Nizhyn, Ukraine|Institute of Pharmacology and Toxicology, National Academy of Medical Sciences, Kyiv, Ukraine

Description

New 3-hydroxy-1,3-diaryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides have been designed, synthesized, and characterized by 1Н NMR, 13C NMR, and LCMS. The cyclic structure of the condensation products of aryl-(3,4,5,6-tetahydropyridin-2-yl)amines with α-bromoketones has been proven. It has been shown that heating 3-hydroxy-1,3-bis-(41-methoxyphenyl)-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide in acetic anhydride accompanied by elimination of water to form 1,3-bis-(41-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide. Antitumor activity of 1,3-bis-(41-ethoxyphenyl)-3-hydroxy-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide and 1,3-bis-(41-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide have been studied. The fully aromatic imidazo[1,2-a]pyridine-1-ium bromide system was shown to have a higher antitumor effect. According to the screening results, the tested compound showed a significant level of anticancer effect on cancer cells of colon COLO 205 (lgGI50 = -5.35, lgTGI = –4.70 and lgLC50 = –4.19) and melanoma SK-MEL-5 (lgGI50 = –5.57, lgTGI = –4.81 and lgLC50 = –4.17).

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Additional details

Cites
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Has part
Figure: 10.3897/pharmacia.71.e135992.figure1 (DOI)
Figure: 10.3897/pharmacia.71.e135992.figure2 (DOI)
Figure: 10.3897/pharmacia.71.e135992.figure3 (DOI)
Figure: 10.3897/pharmacia.71.e135992.figure4 (DOI)

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