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Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition

The use of copper in medicine has a long history and copper-containing compounds have multiple applications, such as in treating heart disease, arthritis, cancer, parasitic as well as other inflammatory diseases. Here, we investigate structural factors, structure-activity relationship and two mechan...

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Main Authors: Lai, Jing Wei, Maah, Mohd Jamil, Sarip, Rozie, Lim, Yvonne Ai Lian, Tim, Khaw Loke, Ng, Chew Hee
Format: Article
Published: Elsevier 2022
Subjects:
QD Chemistry
Online Access:http://eprints.um.edu.my/41427/
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spelling my.um.eprints.414272023-09-22T04:04:08Z http://eprints.um.edu.my/41427/ Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition Lai, Jing Wei Maah, Mohd Jamil Sarip, Rozie Lim, Yvonne Ai Lian Tim, Khaw Loke Ng, Chew Hee QD Chemistry The use of copper in medicine has a long history and copper-containing compounds have multiple applications, such as in treating heart disease, arthritis, cancer, parasitic as well as other inflammatory diseases. Here, we investigate structural factors, structure-activity relationship and two mechanisms of action of a series of copper(II) complexes with 1,10-phenanthroline (phen) and/or amino acid ligands towards Plasmodium falciparum (Pf) 3D7 and artemisinin-resistant Pf5202. To achieve this, the following set of copper(II) complexes, viz. Cu(phen)Cl-2] 1, Cu(phen)(2) Cl]Cl center dot 2H(2)O 2, Cu(phen)(gly)Cl]center dot 2H(2)O 3, Cu(phen)(edda)]center dot 5H(2)O 4, cis-Cu(gly)(2)(H2O)] 5 and Cu(edda)] 6, (gly = glycine; edda = ethylenediamine-N,N'-diacetic acid) were selected, synthesized and characterized by FTIR, elemental analysis, UV-Visible spectroscopy, molar conductivity measurement and magnetic moment. Herein, we report comparison of aqueous copper(II) species, CuCl2 and ligands in inhibiting proteolytic sites of 20S proteasome, generation of reactive oxygen species, hemolysis and antimalarial property. Factors affecting their antimalarial potency are different from those affecting proteasome inhibition and ROS production. Complexes 1 - 4, with IC50 values of about 3 hM towards Pf3D7, were more effective against artemisinin-resistant strain Pf5202 than chloroquine and artemisinin. Evidence of apoptosis of malaria parasite in red blood cells is also presented. (C) 2022 Elsevier B.V. All rights reserved. Elsevier 2022-11 Article PeerReviewed Lai, Jing Wei and Maah, Mohd Jamil and Sarip, Rozie and Lim, Yvonne Ai Lian and Tim, Khaw Loke and Ng, Chew Hee (2022) Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition. Journal of Molecular Structure, 1267. ISSN 0022-2860, DOI https://doi.org/10.1016/j.molstruc.2022.133588 <https://doi.org/10.1016/j.molstruc.2022.133588>. 10.1016/j.molstruc.2022.133588
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic QD Chemistry
spellingShingle QD Chemistry
Lai, Jing Wei
Maah, Mohd Jamil
Sarip, Rozie
Lim, Yvonne Ai Lian
Tim, Khaw Loke
Ng, Chew Hee
Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
description The use of copper in medicine has a long history and copper-containing compounds have multiple applications, such as in treating heart disease, arthritis, cancer, parasitic as well as other inflammatory diseases. Here, we investigate structural factors, structure-activity relationship and two mechanisms of action of a series of copper(II) complexes with 1,10-phenanthroline (phen) and/or amino acid ligands towards Plasmodium falciparum (Pf) 3D7 and artemisinin-resistant Pf5202. To achieve this, the following set of copper(II) complexes, viz. Cu(phen)Cl-2] 1, Cu(phen)(2) Cl]Cl center dot 2H(2)O 2, Cu(phen)(gly)Cl]center dot 2H(2)O 3, Cu(phen)(edda)]center dot 5H(2)O 4, cis-Cu(gly)(2)(H2O)] 5 and Cu(edda)] 6, (gly = glycine; edda = ethylenediamine-N,N'-diacetic acid) were selected, synthesized and characterized by FTIR, elemental analysis, UV-Visible spectroscopy, molar conductivity measurement and magnetic moment. Herein, we report comparison of aqueous copper(II) species, CuCl2 and ligands in inhibiting proteolytic sites of 20S proteasome, generation of reactive oxygen species, hemolysis and antimalarial property. Factors affecting their antimalarial potency are different from those affecting proteasome inhibition and ROS production. Complexes 1 - 4, with IC50 values of about 3 hM towards Pf3D7, were more effective against artemisinin-resistant strain Pf5202 than chloroquine and artemisinin. Evidence of apoptosis of malaria parasite in red blood cells is also presented. (C) 2022 Elsevier B.V. All rights reserved.
format Article
author Lai, Jing Wei
Maah, Mohd Jamil
Sarip, Rozie
Lim, Yvonne Ai Lian
Tim, Khaw Loke
Ng, Chew Hee
author_facet Lai, Jing Wei
Maah, Mohd Jamil
Sarip, Rozie
Lim, Yvonne Ai Lian
Tim, Khaw Loke
Ng, Chew Hee
author_sort Lai, Jing Wei
title Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
title_short Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
title_full Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
title_fullStr Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
title_full_unstemmed Potency of copper(II) complexes towards drug-sensitive and -resistant Plasmodium falciparum: Structure-activity relationship, ROS-generation and proteasome inhibition
title_sort potency of copper(ii) complexes towards drug-sensitive and -resistant plasmodium falciparum: structure-activity relationship, ros-generation and proteasome inhibition
publisher Elsevier
publishDate 2022
url http://eprints.um.edu.my/41427/
_version_ 1778161671056916480
score 13.211869

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