Synthesis and Cytotoxicities of New Azafluorenones with Apoptotic Mechanism of Action and Cell Cycle Analysis

Background: In this study, new azafluorenones, 4-(4-fluorophenyl)-2-(4-substitutedphenyl)-5Hindeno[ 1,2-b] pyridin-5-one, I1-I8 were synthesized and chemical structures were elucidated by spectral analysis. All compounds were reported for the first time here.

Method: Compounds were tested in terms of cytotoxicity. They were found as cytotoxins/anticancer compounds.

Results: It was found that the lead compounds of the series were I5 and I8 according to SI, TS, PSE calculations. When PSE values were considered, compound I5 having chlorine had the highest PSE value of 126.4. Second highest PSE value of 50.5 belonged to I8, which had thiophene ring in its chemical structure. I8 as a representative compound of the series was forwarded to cell cycle analysis. I8 arrested S phase of the cell cycle and lead to apoptosis by inducing PARP cleavage suggesting that at least one of the mechanisms of cytotoxic action of the series was apoptosis.

Conclusion: It was clearly demonstrated that compound I8 can induce early apoptosis at a concentration of 5 µM. The compounds I5 and I8 can be considered as lead compounds of the series with the highest SI, TS, PSE values for further studies.

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