Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer

• 영문명: Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yu Jin Hwang Mi Lyang Chung Uy Dong Sohn Chaeuk Im
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제17권 제6호, 517~524쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2013.01.01

영문 초록

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_-60), and prostate cancer (PC_-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 IC₅₀ 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_-QSAR) models as indicated by the high PLS parameters of the HeLa (q², 0.857; r², 0.984; r2pred, 0.966), HL_-60 (q², 0.777; r², 0.937; r²_pred, 0.913), and PC_-3 (q², 0.702; r², 0.983; r²_pred, 0.974) cell lines. The 3D_-QSAR contour maps suggested that the C-1 NH and C-4 carbonyl group of the naphthyridine ring and the C_-2 naphthyl ring were important for cytotoxicity in all three human cancer cell lines.

키워드

Cytotoxicity Naphthyridine SAR