Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplasti...
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Autor*in:	Praveen K. Roayapalley [verfasserIn] Jonathan R. Dimmock [verfasserIn] Lisett Contreras [verfasserIn] Karol S. Balderrama [verfasserIn] Renato J. Aguilera [verfasserIn] Hiroshi Sakagami [verfasserIn] Shigeru Amano [verfasserIn] Rajendra K. Sharma [verfasserIn] Umashankar Das [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts

Übergeordnetes Werk:	In: Molecules - MDPI AG, 2003, 26(2021), 23, p 7132
Übergeordnetes Werk:	volume:26 ; year:2021 ; number:23, p 7132

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/molecules26237132

Katalog-ID:	DOAJ015916642

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allfields	10.3390/molecules26237132 doi (DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067 DE-627 ger DE-627 rakwb eng QD241-441 Praveen K. Roayapalley verfasserin aut Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties. cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry Jonathan R. Dimmock verfasserin aut Lisett Contreras verfasserin aut Karol S. Balderrama verfasserin aut Renato J. Aguilera verfasserin aut Hiroshi Sakagami verfasserin aut Shigeru Amano verfasserin aut Rajendra K. Sharma verfasserin aut Umashankar Das verfasserin aut In Molecules MDPI AG, 2003 26(2021), 23, p 7132 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:23, p 7132 https://doi.org/10.3390/molecules26237132 kostenfrei https://doaj.org/article/8490478a5d1744f79d0769911a267067 kostenfrei https://www.mdpi.com/1420-3049/26/23/7132 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 23, p 7132
spelling	10.3390/molecules26237132 doi (DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067 DE-627 ger DE-627 rakwb eng QD241-441 Praveen K. Roayapalley verfasserin aut Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties. cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry Jonathan R. Dimmock verfasserin aut Lisett Contreras verfasserin aut Karol S. Balderrama verfasserin aut Renato J. Aguilera verfasserin aut Hiroshi Sakagami verfasserin aut Shigeru Amano verfasserin aut Rajendra K. Sharma verfasserin aut Umashankar Das verfasserin aut In Molecules MDPI AG, 2003 26(2021), 23, p 7132 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:23, p 7132 https://doi.org/10.3390/molecules26237132 kostenfrei https://doaj.org/article/8490478a5d1744f79d0769911a267067 kostenfrei https://www.mdpi.com/1420-3049/26/23/7132 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 23, p 7132
allfields_unstemmed	10.3390/molecules26237132 doi (DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067 DE-627 ger DE-627 rakwb eng QD241-441 Praveen K. Roayapalley verfasserin aut Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties. cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry Jonathan R. Dimmock verfasserin aut Lisett Contreras verfasserin aut Karol S. Balderrama verfasserin aut Renato J. Aguilera verfasserin aut Hiroshi Sakagami verfasserin aut Shigeru Amano verfasserin aut Rajendra K. Sharma verfasserin aut Umashankar Das verfasserin aut In Molecules MDPI AG, 2003 26(2021), 23, p 7132 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:23, p 7132 https://doi.org/10.3390/molecules26237132 kostenfrei https://doaj.org/article/8490478a5d1744f79d0769911a267067 kostenfrei https://www.mdpi.com/1420-3049/26/23/7132 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 23, p 7132
allfieldsGer	10.3390/molecules26237132 doi (DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067 DE-627 ger DE-627 rakwb eng QD241-441 Praveen K. Roayapalley verfasserin aut Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties. cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry Jonathan R. Dimmock verfasserin aut Lisett Contreras verfasserin aut Karol S. Balderrama verfasserin aut Renato J. Aguilera verfasserin aut Hiroshi Sakagami verfasserin aut Shigeru Amano verfasserin aut Rajendra K. Sharma verfasserin aut Umashankar Das verfasserin aut In Molecules MDPI AG, 2003 26(2021), 23, p 7132 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:23, p 7132 https://doi.org/10.3390/molecules26237132 kostenfrei https://doaj.org/article/8490478a5d1744f79d0769911a267067 kostenfrei https://www.mdpi.com/1420-3049/26/23/7132 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 23, p 7132
allfieldsSound	10.3390/molecules26237132 doi (DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067 DE-627 ger DE-627 rakwb eng QD241-441 Praveen K. Roayapalley verfasserin aut Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties. cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry Jonathan R. Dimmock verfasserin aut Lisett Contreras verfasserin aut Karol S. Balderrama verfasserin aut Renato J. Aguilera verfasserin aut Hiroshi Sakagami verfasserin aut Shigeru Amano verfasserin aut Rajendra K. Sharma verfasserin aut Umashankar Das verfasserin aut In Molecules MDPI AG, 2003 26(2021), 23, p 7132 (DE-627)311313132 (DE-600)2008644-1 14203049 nnns volume:26 year:2021 number:23, p 7132 https://doi.org/10.3390/molecules26237132 kostenfrei https://doaj.org/article/8490478a5d1744f79d0769911a267067 kostenfrei https://www.mdpi.com/1420-3049/26/23/7132 kostenfrei https://doaj.org/toc/1420-3049 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2021 23, p 7132
language	English
source	In Molecules 26(2021), 23, p 7132 volume:26 year:2021 number:23, p 7132
sourceStr	In Molecules 26(2021), 23, p 7132 volume:26 year:2021 number:23, p 7132
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts Organic chemistry
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container_title	Molecules
authorswithroles_txt_mv	Praveen K. Roayapalley @@aut@@ Jonathan R. Dimmock @@aut@@ Lisett Contreras @@aut@@ Karol S. Balderrama @@aut@@ Renato J. Aguilera @@aut@@ Hiroshi Sakagami @@aut@@ Shigeru Amano @@aut@@ Rajendra K. Sharma @@aut@@ Umashankar Das @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Praveen K. Roayapalley
spellingShingle	Praveen K. Roayapalley misc QD241-441 misc cytotoxins misc mitochondrial membrane potential misc QSAR misc conjugated unsaturated ketones misc oximes misc quaternary ammonium salts misc Organic chemistry Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts
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topic_title	QD241-441 Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts cytotoxins mitochondrial membrane potential QSAR conjugated unsaturated ketones oximes quaternary ammonium salts
topic	misc QD241-441 misc cytotoxins misc mitochondrial membrane potential misc QSAR misc conjugated unsaturated ketones misc oximes misc quaternary ammonium salts misc Organic chemistry
topic_unstemmed	misc QD241-441 misc cytotoxins misc mitochondrial membrane potential misc QSAR misc conjugated unsaturated ketones misc oximes misc quaternary ammonium salts misc Organic chemistry
topic_browse	misc QD241-441 misc cytotoxins misc mitochondrial membrane potential misc QSAR misc conjugated unsaturated ketones misc oximes misc quaternary ammonium salts misc Organic chemistry
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title	Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts
ctrlnum	(DE-627)DOAJ015916642 (DE-599)DOAJ8490478a5d1744f79d0769911a267067
title_full	Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts
author_sort	Praveen K. Roayapalley
journal	Molecules
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author_browse	Praveen K. Roayapalley Jonathan R. Dimmock Lisett Contreras Karol S. Balderrama Renato J. Aguilera Hiroshi Sakagami Shigeru Amano Rajendra K. Sharma Umashankar Das
container_volume	26
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author-letter	Praveen K. Roayapalley
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title_sort	design, synthesis and tumour-selective toxicity of novel 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes and related quaternary ammonium salts
callnumber	QD241-441
title_auth	Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts
abstract	A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties.
abstractGer	A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties.
abstract_unstemmed	A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes <b<3a</b<–<b<h</b< and related quaternary ammonium salts <b<4a</b<–<b<h</b< were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series <b<3</b< and <b<4</b< to be potent cytotoxins with submicromolar CC<sub<50</sub< values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, <b<3a</b<–<b<h</b< are cytotoxic towards a number of leukemic and colon cancer cells. <b<4b</b<,<b<c</b< lowered the mitochondrial membrane potential in CEM cells, and <b<4d</b< induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely <b<3c</b<,<b<d</b< and <b<4c–e</b<, were identified as lead molecules that have drug-like properties.
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container_issue	23, p 7132
title_short	Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts
url	https://doi.org/10.3390/molecules26237132 https://doaj.org/article/8490478a5d1744f79d0769911a267067 https://www.mdpi.com/1420-3049/26/23/7132 https://doaj.org/toc/1420-3049
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author2	Jonathan R. Dimmock Lisett Contreras Karol S. Balderrama Renato J. Aguilera Hiroshi Sakagami Shigeru Amano Rajendra K. Sharma Umashankar Das
author2Str	Jonathan R. Dimmock Lisett Contreras Karol S. Balderrama Renato J. Aguilera Hiroshi Sakagami Shigeru Amano Rajendra K. Sharma Umashankar Das
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up_date	2024-07-03T17:52:46.858Z
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Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts

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