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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |