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Pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5-amines as Potential Cytotoxic Agents against Human Neuroblastoma.

ABSTRACT: We report herein the evaluation of various pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5-amines as potential cytotoxic agents. These molecules were obtained by developing the multicomponent Groebke-Blackburn-Bienaymé reaction to yield various pyrido[2',1':2,3]imidazo[4,5-c]quinolines which are isosteres of ellipticine whose biological activities are well established. To evaluate the anticancer potential of these pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5-amine derivatives in the human neuroblastoma cell line, the cytotoxicity was examined using the WST-1 assay after 72 h drug exposure. A clonogenic assay was used to assess the ability of treated cells to proliferate and form colonies. Protein expressions (Bax, bcl-2, cleaved caspase-3, cleaved PARP-1) were analyzed using Western blotting. The colony number decrease in cells was 50.54%, 37.88% and 27.12% following exposure to compounds 2d, 2g and 4b respectively at 10 μM. We also show that treating the neuroblastoma cell line with these compounds resulted in a significant alteration in caspase-3 and PARP-1 cleavage.

SUBMITTER: Tber Z

PROVIDER: S-EPMC8399734 | biostudies-literature |

REPOSITORIES: biostudies-literature

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6-Benzyl-3,4-dimeth-oxy-10-methyl-pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-one.

Project description:Pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-ones such as the title compound, C(24)H(21)N(3)O(3), can be obtained in a few minutes in a microwave-assisted three-component reaction from 2-amino-pyridines, isocyanides and 2-carboxy-benz-aldehydes. In the title compound, the pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is almost planar (mean deviation 0.068?Å). The dihedral angle between the benzyl ring and the pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5(6H)-one ring system is 78.2°. The crystal structure is stabilized by inter-molecular C-H?O and C-H?N hydrogen bonds.

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Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines.

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Project description:Continuing our research in the field of new heterocyclic compounds, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3',2':4,5](furo)thieno[3,2-d]pyrimidines as well as of two new heterocyclic systems: furo[2-e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine. Thus, by refluxing the 8-chloro derivatives of pyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidines with various amines, the relevant pyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-8-amines were obtained. Further, the cyclization of some amines under the action of phosphorus oxychloride led to the formation of new heterorings: imidazo[1,2-c]pyrimidine and pyrimido[1,2-c]pyrimidine. The possible antitumor activity of the newly synthesized compounds was evaluated in vitro. The biological tests evidenced that some of them showed pronounced antitumor activity. A study of the structure-activity relationships revealed that the compound activity depended mostly on the nature of the amine fragments. A docking analysis was also performed for the most active compounds.

| S-EPMC6864781 | biostudies-literature

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