Detecting early-stage ovarian cancer, the fourth leading cause of cancerrelated
deaths in women, is difficult, and the development of novel chemotherapeutic
agents is required. Since several flavonoids show anticancer activities against ovarian cancer, 35 naphthylated flavonoids
including 3’,4’-naphthochalcones, 5’,6’-naphthochalcone, 7,8-nap-hthoflavones, 5,6-naphthoflavanones, 5,6-naphthoflavones,
2,3-naphthochalcone, N-phenylpyrazolyl-5’,6’-naphthocha-lcones, carbothioamidepyrazolyl-5’,6’-naphthochalcones,
pyrazolyl-3’,4’-naphthochalcone, and carbothioamidepyrazolyl-3’,4’-naphthochalcone were designed and synthesized.
To explore the anticancer effects of these compounds, clonogenic long-term survival assays were applied on human
cisplatin-resistant A2780/Cis ovarian cancer cells. Relationships between the structural properties of 35 naphthylated flavonoids
and their clonogenicities were explored using comparative molecular field analysis and hologram quantitative structure–
activity relationships. As a result, several structural features that increased cell growth inhibitory activity were identified, and
a compound satisfying these conditions, 5-(2,3-dimethoxyphenyl)-3-(1-hydroxynaphthalen-2-yl)-N-phenyl-4,5-dihydro-1Hpyrazole-
1-carbothioamide, was designed and synthesized. This novel compound´s half-maximal cell growth inhibitory concentration
was lower than those of the 35 flavonoid derivatives tested here. Therefore, the structural features observed in this
report can be used to design and develop potent chemotherapeutic agents to treat ovarian cancer cells.