Korean J Physiol Pharmacol. 2013 Dec;17(6):517-23. doi: 10.4196/kjpp.2013.17.6.517. Epub 2013 Dec 16.

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

The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology

Yu Jin Hwang, Mi Lyang Chung, Uy Dong Sohn, Chaeuk Im

PMID: 24381501 PMCID: PMC3874439 DOI: 10.4196/kjpp.2013.17.6.517

Abstract

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 (q(2), 0.857; r(2), 0.984; r(2) pred, 0.966), HL-60 (q(2), 0.777; r(2), 0.937; r(2) pred, 0.913), and PC-3 (q(2), 0.702; r(2), 0.983; r(2) 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.

Keywords: Cytotoxicity; Naphthyridine; SAR

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