Cargando…

Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties

Novel purine and purine isosteres containing a ferrocene motif and 4,1-disubstituted (11a−11c, 12a−12c, 13a−13c, 14a−14c, 15a−15c, 16a, 23a−23c, 24a−24c, 25a−25c) and 1,4-disubstituted (34a−34c and 35a−35c) 1,2,3-triazole rings were synthesized. The most potent cytotoxic effect on colorectal adenoca...

Descripción completa

Detalles Bibliográficos
Autores principales: Rep, Valentina, Piškor, Martina, Šimek, Helena, Mišetić, Petra, Grbčić, Petra, Padovan, Jasna, Gabelica Marković, Vesna, Jadreško, Dijana, Pavelić, Krešimir, Kraljević Pavelić, Sandra, Raić-Malić, Silvana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180452/
https://www.ncbi.nlm.nih.gov/pubmed/32235404
http://dx.doi.org/10.3390/molecules25071570
_version_ 1783525822680793088
author Rep, Valentina
Piškor, Martina
Šimek, Helena
Mišetić, Petra
Grbčić, Petra
Padovan, Jasna
Gabelica Marković, Vesna
Jadreško, Dijana
Pavelić, Krešimir
Kraljević Pavelić, Sandra
Raić-Malić, Silvana
author_facet Rep, Valentina
Piškor, Martina
Šimek, Helena
Mišetić, Petra
Grbčić, Petra
Padovan, Jasna
Gabelica Marković, Vesna
Jadreško, Dijana
Pavelić, Krešimir
Kraljević Pavelić, Sandra
Raić-Malić, Silvana
author_sort Rep, Valentina
collection PubMed
description Novel purine and purine isosteres containing a ferrocene motif and 4,1-disubstituted (11a−11c, 12a−12c, 13a−13c, 14a−14c, 15a−15c, 16a, 23a−23c, 24a−24c, 25a−25c) and 1,4-disubstituted (34a−34c and 35a−35c) 1,2,3-triazole rings were synthesized. The most potent cytotoxic effect on colorectal adenocarcinoma (SW620) was exerted by the 6-chloro-7-deazapurine 11c (IC(50) = 9.07 µM), 6-chloropurine 13a (IC(50) = 14.38 µM) and 15b (IC(50) = 15.50 µM) ferrocenylalkyl derivatives. The N-9 isomer of 6-chloropurine 13a containing ferrocenylmethylene unit showed a favourable in vitro physicochemical and ADME properties including high solubility, moderate permeability and good metabolic stability in human liver microsomes.
format Online
Article
Text
id pubmed-7180452
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71804522020-05-01 Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties Rep, Valentina Piškor, Martina Šimek, Helena Mišetić, Petra Grbčić, Petra Padovan, Jasna Gabelica Marković, Vesna Jadreško, Dijana Pavelić, Krešimir Kraljević Pavelić, Sandra Raić-Malić, Silvana Molecules Article Novel purine and purine isosteres containing a ferrocene motif and 4,1-disubstituted (11a−11c, 12a−12c, 13a−13c, 14a−14c, 15a−15c, 16a, 23a−23c, 24a−24c, 25a−25c) and 1,4-disubstituted (34a−34c and 35a−35c) 1,2,3-triazole rings were synthesized. The most potent cytotoxic effect on colorectal adenocarcinoma (SW620) was exerted by the 6-chloro-7-deazapurine 11c (IC(50) = 9.07 µM), 6-chloropurine 13a (IC(50) = 14.38 µM) and 15b (IC(50) = 15.50 µM) ferrocenylalkyl derivatives. The N-9 isomer of 6-chloropurine 13a containing ferrocenylmethylene unit showed a favourable in vitro physicochemical and ADME properties including high solubility, moderate permeability and good metabolic stability in human liver microsomes. MDPI 2020-03-29 /pmc/articles/PMC7180452/ /pubmed/32235404 http://dx.doi.org/10.3390/molecules25071570 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rep, Valentina
Piškor, Martina
Šimek, Helena
Mišetić, Petra
Grbčić, Petra
Padovan, Jasna
Gabelica Marković, Vesna
Jadreško, Dijana
Pavelić, Krešimir
Kraljević Pavelić, Sandra
Raić-Malić, Silvana
Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title_full Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title_fullStr Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title_full_unstemmed Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title_short Purine and Purine Isostere Derivatives of Ferrocene: An Evaluation of ADME, Antitumor and Electrochemical Properties
title_sort purine and purine isostere derivatives of ferrocene: an evaluation of adme, antitumor and electrochemical properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180452/
https://www.ncbi.nlm.nih.gov/pubmed/32235404
http://dx.doi.org/10.3390/molecules25071570
work_keys_str_mv AT repvalentina purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT piskormartina purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT simekhelena purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT miseticpetra purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT grbcicpetra purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT padovanjasna purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT gabelicamarkovicvesna purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT jadreskodijana purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT pavelickresimir purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT kraljevicpavelicsandra purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties
AT raicmalicsilvana purineandpurineisosterederivativesofferroceneanevaluationofadmeantitumorandelectrochemicalproperties