Repozytorium

New Hydrazone Derivatives Based on Pyrazolopyridothiazine Core as Cytotoxic Agents to Colon Cancers: Design, Synthesis, Biological Evaluation, and Molecular Modeling

Autorzy

Teresa Glomb

Kamila Środa-Pomianek

Anna Palko-Łabuz

Olga Wesołowska

Agnieszka Wikiera

Kamil Wojtkowiak

Aneta Jezierska

Andrzej Kochel

Roman Lesyk

Piotr Świątek

Rok wydania

2025

Czasopismo

ChemMedChem

Numer woluminu

20

Strony

e202400687/1-e202400687/19

DOI

10.1002/cmdc.202400687

Kolekcja

Naukowa

Język

Angielski

Typ publikacji

Artykuł

Streszczenie

In this research, a series of novel hydrazone derivatives based on pyrazolopyridothiazinylacetohydrazide were designed, synthesized, and evaluated for their in vitro cytotoxic potency on several human colon cancer cells (HTC116, HT-29, and LoVo). After MTT and SRB assays four of the most active derivatives: hydrazide GH and hydrazones GH7GH8, and GH11, were chosen for further investigation. Hydrazone GH11 had the highest cytotoxic activity (IC50 values of c.a. 0.5 μM). Additionally, the impact of novel derivatives on the oxidative stress level, apoptosis induction, and modulation of inflammation in colon cancer cells was examined. In all studies, the activity of the derivatives increased in order GH < GH7 < GH8 < GH11. At the same time, most of the research was conducted on compounds combined with apple pectin (PC). The most interesting observation was that all the studied derivatives applied together with PC showed significantly higher activity than observed in the case of using PC, hydrazide, or hydrazones separately. Finally, computational chemistry methods (molecular modeling and Density Functional Theory – DFT) were used to complement the experimental studies.

Słowa kluczowe

pyrazolopyridothiazinylacetohydrazide, hydrazones, colon cancer, cytotoxic activity, molecular modeling

Adres publiczny

http://dx.doi.org/10.1002/cmdc.202400687

Strona internetowa wydawcy

https://onlinelibrary.wiley.com/

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