Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells

B13 analogues are being considered as therapeutic agents for cancer cells, since B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer cells. B13 sulfonamides are assumed to have biological activity similar to B13, since they are made by bioisosterically substituting the...

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Main Authors:	Lee, Seul Ki Chan, Park, Sang Min, Im, Chaeuk
Format:	Online
Language:	English
Published:	The Korean Physiological Society and The Korean Society of Pharmacology 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282231/

id	pubmed-3282231
recordtype	oai_dc
spelling	pubmed-32822312012-02-22 Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells Lee, Seul Ki Chan Park, Sang Min Im, Chaeuk Original Article B13 analogues are being considered as therapeutic agents for cancer cells, since B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer cells. B13 sulfonamides are assumed to have biological activity similar to B13, since they are made by bioisosterically substituting the carboxyl moiety of B13 with sulfone group. Twenty B13 sulfonamides were evaluated for their in vitro cytotoxicities against human colon cancer HT-29 and lung cancer A549 cell lines using MTT assays. Replacement of the amide group with a sulfonamide group increased cytotoxicity in both cancer cell lines. The sulfonamides with long alkyl chains exhibited activities two to three times more potent than that of B13 and compound (15) had the most potent activity with IC50 values of 27 and 28.7µM for HT-29 and A549, respectively. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to carry out QSAR molecular modeling of these compounds. The predictive CoMSIA models for HT-29 and A549 gave cross-validated q2 values of 0.703 and 0.830, respectively. From graphical analysis of these models, we suppose that the stereochemistry of 1,3-propandiol is not important for activity and that introduction of a sulfonamide group and long alkyl chains into B13 can increase cytotoxicity. The Korean Physiological Society and The Korean Society of Pharmacology 2011-12 2011-12-27 /pmc/articles/PMC3282231/ /pubmed/22359481 http://dx.doi.org/10.4196/kjpp.2011.15.6.423 Text en Copyright © 2011 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	Lee, Seul Ki Chan Park, Sang Min Im, Chaeuk
spellingShingle	Lee, Seul Ki Chan Park, Sang Min Im, Chaeuk Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
author_facet	Lee, Seul Ki Chan Park, Sang Min Im, Chaeuk
author_sort	Lee, Seul Ki Chan
title	Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
title_short	Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
title_full	Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
title_fullStr	Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
title_full_unstemmed	Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells
title_sort	cytotoxicities and quantitative structure activity relationships of b13 sulfonamides in ht-29 and a549 cells
description	B13 analogues are being considered as therapeutic agents for cancer cells, since B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer cells. B13 sulfonamides are assumed to have biological activity similar to B13, since they are made by bioisosterically substituting the carboxyl moiety of B13 with sulfone group. Twenty B13 sulfonamides were evaluated for their in vitro cytotoxicities against human colon cancer HT-29 and lung cancer A549 cell lines using MTT assays. Replacement of the amide group with a sulfonamide group increased cytotoxicity in both cancer cell lines. The sulfonamides with long alkyl chains exhibited activities two to three times more potent than that of B13 and compound (15) had the most potent activity with IC50 values of 27 and 28.7µM for HT-29 and A549, respectively. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to carry out QSAR molecular modeling of these compounds. The predictive CoMSIA models for HT-29 and A549 gave cross-validated q2 values of 0.703 and 0.830, respectively. From graphical analysis of these models, we suppose that the stereochemistry of 1,3-propandiol is not important for activity and that introduction of a sulfonamide group and long alkyl chains into B13 can increase cytotoxicity.
publisher	The Korean Physiological Society and The Korean Society of Pharmacology
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282231/
_version_	1611506944100532224

Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells

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