İrem Durmaz Şahin

Targeting Ovarian Cancer With Pyrimidine Nucleobase and Nucleoside Analogs: Synthesis, In Vitro Cytotoxic Activity, and Molecular Docking

ABSTRACT Ovarian cancer remains one of the most lethal gynecological malignancies, underscoring the need for novel therapeutic strategies. In this study, a series of pyrimidine‐based nucleobase ( 7–14 ) and nucleoside ( 21–24 ) analogs were synthesized and evaluated for their potential anticancer activity through poly(ADP‐ribose) polymerase (PARP) inhibition. These compounds were tested for in vitro cytotoxicity on ovarian cancer cell lines OVCAR‐3 and KURAMOCHI. Among the synthesized derivatives—namely, 4‐(4‐substituted phenylamino)‐1‐cyclopentyl‐5‐( H /methyl)pyrimidine‐2(1 H )‐ones ( 7–14 ) and 4‐(4‐substituted phenylamino)‐1‐(β‐ d ‐ribofuranosyl)‐5‐methylpyrimidine‐2(1 H )‐ones ( 21–24 )—compound 8 exhibited the most potent cytotoxic activity. It significantly reduced cell viability in OVCAR‐3 (IC 50  = 27.1 ± 4.56 µM) and KURAMOCHI (IC 50  = 46.2 ± 4.87 µM) cells, outperforming the reference PARP inhibitor olaparib (IC 50  = 75.8 ± 6.1 µM for OVCAR‐3, IC 50  = 84.5 ± 11.4 µM for KURAMOCHI). These results suggest that compound 8 is a promising lead candidate for further development as an anticancer agent targeting PARP in ovarian cancer.

Targeting Ovarian Cancer with Chalcone Derivatives: Cytotoxicity and Apoptosis Induction in HGSOC Cells

Ovarian cancer ranks as the eighth most prevalent form of cancer in women across the globe and stands as the third most frequent gynecological cancer, following cervical and endometrial cancers. Given its resistance to standard chemotherapy and high recurrence rates, there is an urgent imperative to discover novel compounds with potential as chemotherapeutic agents for treating ovarian cancer. Chalcones exhibit a wide array of biological properties, with a particular focus on their anti-cancer activities. In this research, we documented the synthesis and in vitro study of a small library of chalcone derivatives designed for use against high-grade serous ovarian cancer (HGSOC) cell lines, specifically OVCAR-3, OVSAHO, and KURAMOCHI. Our findings revealed that three of these compounds exhibited cytotoxic and anti-proliferative effects against all the tested HGSOC cell lines, achieving IC50 concentrations lower than 25 µM. Further investigations disclosed that these chalcones prompted an increase in the subG1 phase cell cycle and induced apoptosis in OVCAR-3 cells. In summary, our study underscores the potential of chalcones as promising agents for the treatment of ovarian cancer.