Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.

Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resista...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maciej Serda, Danuta S Kalinowski, Nathalie Rasko, Eliška Potůčková, Anna Mrozek-Wilczkiewicz, Robert Musiol, Jan G Małecki, Mieczysław Sajewicz, Alicja Ratuszna, Angelika Muchowicz, Jakub Gołąb, Tomáš Simůnek, Des R Richardson, Jaroslaw Polanski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a9dc547c1614e48ab4038b68ed48796
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8a9dc547c1614e48ab4038b68ed48796
record_format	dspace
spelling	oai:doaj.org-article:8a9dc547c1614e48ab4038b68ed487962021-11-25T05:56:20ZExploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.1932-620310.1371/journal.pone.0110291https://doaj.org/article/8a9dc547c1614e48ab4038b68ed487962014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0110291https://doaj.org/toc/1932-6203Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized "soft" donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.Maciej SerdaDanuta S KalinowskiNathalie RaskoEliška PotůčkováAnna Mrozek-WilczkiewiczRobert MusiolJan G MałeckiMieczysław SajewiczAlicja RatusznaAngelika MuchowiczJakub GołąbTomáš SimůnekDes R RichardsonJaroslaw PolanskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e110291 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maciej Serda Danuta S Kalinowski Nathalie Rasko Eliška Potůčková Anna Mrozek-Wilczkiewicz Robert Musiol Jan G Małecki Mieczysław Sajewicz Alicja Ratuszna Angelika Muchowicz Jakub Gołąb Tomáš Simůnek Des R Richardson Jaroslaw Polanski Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
description	Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized "soft" donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.
format	article
author	Maciej Serda Danuta S Kalinowski Nathalie Rasko Eliška Potůčková Anna Mrozek-Wilczkiewicz Robert Musiol Jan G Małecki Mieczysław Sajewicz Alicja Ratuszna Angelika Muchowicz Jakub Gołąb Tomáš Simůnek Des R Richardson Jaroslaw Polanski
author_facet	Maciej Serda Danuta S Kalinowski Nathalie Rasko Eliška Potůčková Anna Mrozek-Wilczkiewicz Robert Musiol Jan G Małecki Mieczysław Sajewicz Alicja Ratuszna Angelika Muchowicz Jakub Gołąb Tomáš Simůnek Des R Richardson Jaroslaw Polanski
author_sort	Maciej Serda
title	Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
title_short	Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
title_full	Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
title_fullStr	Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
title_full_unstemmed	Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
title_sort	exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8a9dc547c1614e48ab4038b68ed48796
work_keys_str_mv	AT maciejserda exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT danutaskalinowski exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT nathalierasko exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT eliskapotuckova exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT annamrozekwilczkiewicz exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT robertmusiol exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT jangmałecki exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT mieczysławsajewicz exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT alicjaratuszna exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT angelikamuchowicz exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT jakubgołab exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT tomassimunek exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT desrrichardson exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships AT jaroslawpolanski exploringtheanticanceractivityofnovelthiosemicarbazonesgeneratedthroughthecombinationofretrofragmentsdissectionofcriticalstructureactivityrelationships
_version_	1718414353464557568

Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.

Ejemplares similares