Synthesis of thiazole-integrated pyrrolotriazinones: evaluations of cytotoxicity and effects on PI3K levels in cancer cells

Authors

EYLEM KUZUFollow
EGE ARZUKFollow
FUAT KARAKUŞFollow
BURAK KUZUFollow
HASAN GENÇFollow

Abstract

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.

Author ORCID Identifier

EYLEM KUZU: 0000-0002-4719-8654

EGE ARZUK: 0000-0002-3239-4855

FUAT KARAKUŞ: 0000-0002-5260-3650

BURAK KUZU: 0000-0002-7305-7177

HASAN GENÇ: 0000-0003-1454-3279

DOI

10.55730/1300-0527.3723

Keywords

Anticancer effect, molecular docking, PI3K, pre-ADMET, pyrrolotriazinone

First Page

215

Last Page

227

Publisher

Scientific and Technological Research Council of Türkiye (TUBITAK)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

KUZU, EYLEM; ARZUK, EGE; KARAKUŞ, FUAT; KUZU, BURAK; and GENÇ, HASAN (2025) "Synthesis of thiazole-integrated pyrrolotriazinones: evaluations of cytotoxicity and effects on PI3K levels in cancer cells," Turkish Journal of Chemistry: Vol. 49: No. 2, Article 8. https://doi.org/10.55730/1300-0527.3723
Available at: https://journals.tubitak.gov.tr/chem/vol49/iss2/8