Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
- Yu Jin Hwang Mi Lyang Chung Uy Dong Sohn Chaeuk Im
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제17권 제6호
- 등재여부 : KCI등재
- 2013.01
- 517 - 524 (8 pages)
Naphthyridine compounds are important, because they exhibit various biological activities including anticancer, antimicrobial, and anti-inflammatory activity. Some naphthyridines have antimitotic effects or demonstrate anticancer activity by inhibiting topoisomerase II. These compounds have been investigated as potential anticancer agents, and several compounds are now part of clinical trials. A series of naphthyridine derivatives were evaluated for their in vitro cytotoxic activities against human cervical cancer (HeLa), leukemia (HL<sub>-</sub>60), and prostate cancer (PC<sub>-</sub>3) cell lines using an MTT assay. Some compounds (14, 15, and 16) were more potent than colchicine against all three human cancer cell lines and compound (16) demonstrated potency with IC<sub>50</sub> values of 0.7, 0.1, and 5.1 μM, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used for quantitative structure-activity relationship (QSAR) molecular modeling of these compounds. We obtained accurate and predictive three-dimensional QSAR (3D<sub>-</sub>QSAR) models as indicated by the high PLS parameters of the HeLa (q<sup>2</sup>, 0.857; r<sup>2</sup>, 0.984; r2pred, 0.966), HL<sub>-</sub>60 (q<sup>2</sup>, 0.777; r<sup>2</sup>, 0.937; r<sup>2</sup><sub>pred</sub>, 0.913), and PC<sub>-</sub>3 (q<sup>2</sup>, 0.702; r<sup>2</sup>, 0.983; r<sup>2</sup><sub>pred</sub>, 0.974) cell lines. The 3D<sub>-</sub>QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C<sub>-</sub>2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.