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. 2024 Aug;85(5):e22229.
doi: 10.1002/ddr.22229.

Preliminary evaluation of antiproliferative and apoptotic activities of novel indolin-2-one derivatives

Gulseren Turhal  1 , Busra Demirkan  1 , Izel Nermin Baslilar  1 , Nimet Sule Yuncu  1 , Sultan Nacak Baytas  2 , Asuman Demiroglu-Zergeroglu  1
Affiliations

Preliminary evaluation of antiproliferative and apoptotic activities of novel indolin-2-one derivatives

Gulseren Turhal et al. Drug Dev Res. 2024 Aug.

Abstract

Indole-based agents are frequently used in targeted or supportive therapy of several cancers. In this study, we investigated the anticancer properties of originally synthesized novel indolin-2-one derivatives (6a-d) against Malignant Mesothelioma, Breast cancer, and Colon Cancer cells. Our results revealed that all derivatives were effectively delayed cell proliferation by inhibiting the ERK1/2, AKT, and STAT3 signaling pathways in a concentration-dependent manner. Additionally, these variants induced cell cycle arrest in the S phase, accompanied by elevated levels of p21 and p27 expressions. Derivatives also initiated mitochondrial apoptosis through the upregulation of Bax and downregulation of Bcl-2 proteins, leading to the activation of caspase 3 and PARP cleavage in exposed cells. Remarkably, three of the indolin-2-one derivatives displayed significant selectivity towards Breast and Colon Cancer cells, with compound 6d promising as the most potent and wide spectral one for all cancer cell lines.

Keywords: breast cancer; malignant mesothelioma; novel indolin‐2‐one.

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