A Novel 2,7-Naphthyridine Derivative Suppresses Ovarian Cancer Cell Growth Through G1 Cell Cycle Arrest, Apoptosis Induction and Migration Inhibition.

Authors

Gabriela Chabowska, Konrad Chabowski, Helena Moreira, Anna Wójcicka, Anna Szyjka, Patrycja Koruba, Dorota Bęben, Tomasz Piasecki, Ewa Barg

Published in

Pharmaceuticals (Basel, Switzerland). Volume 19. Issue 10. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Background/Objectives: Ovarian cancer remains one of the deadliest gynecological malignancies due to late diagnosis, frequent recurrence, and the development of resistance to platinum-based chemotherapy. Naphthyridines constitute a diverse class of heterocyclic compounds with promising anticancer properties. The aim of this study was to evaluate the anticancer activity of three structurally related 2,7-naphthyridine derivatives (Naph-1, Naph-2, and Naph-3), identify the most active compound, and investigate its mechanism of action in ovarian cancer models. Methods: Cytotoxic activity was evaluated using the PrestoBlue assay in human cancer cell lines IGROV-1, MDAH-2774, SKOV-3, K562, MCF-7, and A549 and a non-cancerous CHO-K1 cell line. The most active derivative, Naph-3, was subsequently characterized in the two most sensitive ovarian cancer models (IGROV-1 and MDAH-2774) by evaluating its effects on 3D spheroid viability, cell proliferation, migration, apoptosis, and cell cycle progression. Electrochemical impedance spectroscopy was used as a label-free method for real-time monitoring of treatment-induced cellular responses. Cisplatin served as the reference compound. Results: Among the tested derivatives, Naph-3 demonstrated the strongest anticancer activity, with the highest sensitivity observed in ovarian cancer cell lines IGROV-1 (IC₅₀ 30.31 µM) and MDAH-2774 (IC₅₀ 53.68 µM). Naph-3 inhibited cell proliferation and migration, induced G1-phase cell cycle arrest, and promoted apoptotic cell death in both IGROV-1 and MDAH-2774 cells. In 3D spheroid models, Naph-3 retained significant activity in IGROV-1 spheroids, whereas MDAH-2774 spheroids displayed pronounced resistance to treatment. Although Naph-3 was less potent than cisplatin, it exhibited greater selectivity toward cancer cells, with lower toxicity against non-cancerous CHO-K1 cells. Impedance spectroscopy in a wide frequency range provided complementary kinetic information, supporting the interpretation that Naph-3 exerts a predominantly cytostatic effect, whereas cisplatin induces a more pronounced cytotoxic response. Conclusions: Naph-3 emerged as the most promising derivative among the tested compounds and exhibited multifaceted anticancer activity in IGROV-1 and MDAH-2774 ovarian cancer models. Its favorable selectivity profile, combined with antiproliferative, pro-apoptotic, and anti-migratory properties, highlights its potential as a promising compound for the development of novel therapeutic strategies against ovarian cancer.

PMID:
42943259
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.