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

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 inv...

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Main Authors:	Hwang, Yu Jin, Chung, Mi Lyang, Sohn, Uy Dong, Im, Chaeuk
Format:	Online
Language:	English
Published:	The Korean Physiological Society and The Korean Society of Pharmacology 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874439/

id	pubmed-3874439
recordtype	oai_dc
spelling	pubmed-38744392013-12-31 Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer Hwang, Yu Jin Chung, Mi Lyang Sohn, Uy Dong Im, Chaeuk Original Article 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; r2pred, 0.913), and PC-3 (q2, 0.702; r2, 0.983; r2pred, 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. The Korean Physiological Society and The Korean Society of Pharmacology 2013-12 2013-12-16 /pmc/articles/PMC3874439/ /pubmed/24381501 http://dx.doi.org/10.4196/kjpp.2013.17.6.517 Text en Copyright © 2013 The Korean Physiological Society and The Korean Society of Pharmacology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hwang, Yu Jin Chung, Mi Lyang Sohn, Uy Dong Im, Chaeuk
spellingShingle	Hwang, Yu Jin Chung, Mi Lyang Sohn, Uy Dong Im, Chaeuk Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
author_facet	Hwang, Yu Jin Chung, Mi Lyang Sohn, Uy Dong Im, Chaeuk
author_sort	Hwang, Yu Jin
title	Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
title_short	Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
title_full	Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
title_fullStr	Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
title_full_unstemmed	Cytotoxicity and Structure-activity Relationships of Naphthyridine Derivatives in Human Cervical Cancer, Leukemia, and Prostate Cancer
title_sort	cytotoxicity and structure-activity relationships of naphthyridine derivatives in human cervical cancer, leukemia, and prostate cancer
description	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; r2pred, 0.913), and PC-3 (q2, 0.702; r2, 0.983; r2pred, 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.
publisher	The Korean Physiological Society and The Korean Society of Pharmacology
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874439/
_version_	1612041989258215424

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

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