The in Vitro Antiplasmodial and Antiproliferative ...
Type de document :
Article dans une revue scientifique
DOI :
URL permanente :
Titre :
The in Vitro Antiplasmodial and Antiproliferative Activity of New Ferrocene‐Based α‐Aminocresols Targeting Hemozoin Inhibition and DNA Interaction
Auteur(s) :
Mbaba, Mziyanda [Auteur]
Rhodes University, Grahamstown
Dingle, Laura M. K. [Auteur]
Rhodes University, Grahamstown
Swart, Tarryn [Auteur]
Rhodes University, Grahamstown
Cash, Devon [Auteur]
Rhodes University, Grahamstown
Laming, Dustin [Auteur]
Rhodes University, Grahamstown
de la Mare, Jo‐Anne [Auteur]
Rhodes University, Grahamstown
Taylor, Dale [Auteur]
University of Cape Town
Hoppe, Heinrich C. [Auteur]
Rhodes University, Grahamstown
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Edkins, Adrienne L. [Auteur]
Rhodes University, Grahamstown
Khanye, Setshaba D. [Auteur]
Rhodes University, Grahamstown
Rhodes University, Grahamstown
Dingle, Laura M. K. [Auteur]
Rhodes University, Grahamstown
Swart, Tarryn [Auteur]
Rhodes University, Grahamstown
Cash, Devon [Auteur]
Rhodes University, Grahamstown
Laming, Dustin [Auteur]
Rhodes University, Grahamstown
de la Mare, Jo‐Anne [Auteur]
Rhodes University, Grahamstown
Taylor, Dale [Auteur]
University of Cape Town
Hoppe, Heinrich C. [Auteur]
Rhodes University, Grahamstown
Biot, Christophe [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Edkins, Adrienne L. [Auteur]
Rhodes University, Grahamstown
Khanye, Setshaba D. [Auteur]
Rhodes University, Grahamstown
Titre de la revue :
ChemBioChem
Nom court de la revue :
https://lilloa.univ-lille.fr/handle/20.500.12210/33ChemBioChem
Numéro :
21
Pagination :
2643-2658
Éditeur :
Wiley
Date de publication :
2020-05-27
Mot(s)-clé(s) en anglais :
Aminocresols
breast cancer
DNA interactions
ferrocene
hemozoin inhibition
Plasmodium falciparum
breast cancer
DNA interactions
ferrocene
hemozoin inhibition
Plasmodium falciparum
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation ...
Lire la suite >The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation of potent drug leads in the quest for therapeutic chemotypes with the potential to overcome the development of clinical resistance. Herein, we present the in vitro antiplasmodial and antiproliferative investigation of ferrocenyl α‐aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and an α‐aminocresol scaffold possessing antimalarial activity. The compounds pursued in the study exhibited higher toxicity towards the chemosensitive (3D7) and ‐resistant (Dd2) strains of the Plasmodium falciparum parasite than to the human HCC70 triple‐negative breast cancer cell line. Indication of cross‐resistance was absent for the compounds evaluated against the multi‐resistant Dd2 strain. Structure‐activity analysis revealed that the phenolic hydroxy group and rotatable σ bond between the α‐carbon and NH group of the α‐amino‐o‐cresol skeleton are crucial for the biological activity of the compounds. Spectrophotometric techniques and in silico docking simulations performed on selected derivatives suggest that the compounds show a dual mode of action involving hemozoin inhibition and DNA interaction via minor‐groove binding. Lastly, compound 9 a, identified as a possible lead, exhibited preferential binding for the plasmodial DNA isolated from 3D7 P. falciparum trophozoites over the mammalian calf thymus DNA, thereby substantiating the enhanced antiplasmodial activity of the compounds. The presented research demonstrates the strategy of incorporating organometallic complexes into known biologically active organic scaffolds as a viable avenue to fashion novel multimodal compounds with potential to counter the development drug resistance.Lire moins >
Lire la suite >The conjugation of organometallic complexes to known bioactive organic frameworks is a proven strategy revered for devising new drug molecules with novel modes of action. This approach holds great promise for the generation of potent drug leads in the quest for therapeutic chemotypes with the potential to overcome the development of clinical resistance. Herein, we present the in vitro antiplasmodial and antiproliferative investigation of ferrocenyl α‐aminocresol conjugates assembled by amalgamation of the organometallic ferrocene unit and an α‐aminocresol scaffold possessing antimalarial activity. The compounds pursued in the study exhibited higher toxicity towards the chemosensitive (3D7) and ‐resistant (Dd2) strains of the Plasmodium falciparum parasite than to the human HCC70 triple‐negative breast cancer cell line. Indication of cross‐resistance was absent for the compounds evaluated against the multi‐resistant Dd2 strain. Structure‐activity analysis revealed that the phenolic hydroxy group and rotatable σ bond between the α‐carbon and NH group of the α‐amino‐o‐cresol skeleton are crucial for the biological activity of the compounds. Spectrophotometric techniques and in silico docking simulations performed on selected derivatives suggest that the compounds show a dual mode of action involving hemozoin inhibition and DNA interaction via minor‐groove binding. Lastly, compound 9 a, identified as a possible lead, exhibited preferential binding for the plasmodial DNA isolated from 3D7 P. falciparum trophozoites over the mammalian calf thymus DNA, thereby substantiating the enhanced antiplasmodial activity of the compounds. The presented research demonstrates the strategy of incorporating organometallic complexes into known biologically active organic scaffolds as a viable avenue to fashion novel multimodal compounds with potential to counter the development drug resistance.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
CNRS
Équipe(s) de recherche :
Chemical Glycobiology
Date de dépôt :
2021-01-28T13:36:27Z
2021-02-08T17:37:14Z
2021-02-08T17:37:14Z
Fichiers
- P20.30 The in Vitro Antiplasmodial and Antiproliferative Activity .pdf
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