Browsing by Author "Kuzu, Eylem"

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Synthesis of Thiazole-Integrated Pyrrolotriazinones: Evaluations of Cytotoxicity and Effects on P3ik Levels in Cancer Cells
(Tubitak Scientific & Technological Research Council Turkey, 2025) Kuzu, Eylem; Arzuk, Ege; Karakus, Fuat; Kuzu, Burak; Genc, Hasan
The synthesis of novel heterocyclic compounds, particularly those targeting critical signaling pathways in cancer, represents a promising approach to drug development. In this study, we designed and synthesized a series of thiazole-integrated pyrrolotriazinone derivatives, aiming to combine the antiproliferative properties of thiazole with the PI3K inhibitory activity of pyrrolotriazinones. The PI3K pathway, which plays a critical role in regulating cell growth, proliferation, and survival, is frequently dysregulated in cancer, making it an attractive target for therapeutic intervention. The synthesized derivatives were evaluated for their cytotoxic activities against MCF-7, A549, and HepG2 cancer cell lines. Their effect on PI3K protein levels was assessed to evaluate their potential as PI3K inhibitors. Preliminary results indicate that these thiazole-pyrrolotriazinone hybrids exhibit significant cytotoxic effects and may reduce PI3K protein levels in cancer cells. Furthermore, drug-likeness assessments and pre-ADMET evaluations demonstrated that the compounds exhibited promising characteristics, supporting their potential as viable drug candidates. Overall, this study highlights the potential of these novel compounds in cancer therapy and provides valuable insights into the design of small molecules that can target key regulatory pathways involved in cancer progression.
Tandem Synthesis of Novel Thiazole-Substituted Pyrrolo[1,2-D][1,2,4]triazin Derivatives and Their Theoretical Pharmacokinetic Profiles
(Springer, 2023) Kuzu, Eylem; Kuzu, Burak
In this study, a new tandem method was developed for the synthesis of thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one derivatives. The method consists of a tandem reaction involving a subsequent formation of first the thiazole and then the triazine ring upon the addition of phenacyl bromide to a product of the condensation reaction between ethyl 2-formyl-1H-pyrrole- 1-carboxylate and thiosemicarbazide. The tandem cyclization step was completed in just 30 minutes. In order to predict the reaction mechanism, the charge densities of atoms and HOMO and LUMO energy were calculated by DFT method for the compounds obtained in the intermediate stage. In addition, a series of pyrrolotriazinone derivatives synthesized in high yields by this method were found to be suitable drug candidates according to their druglikeness and theoretical pharmacokinetic profiles.