Exploring antimalarial potential: Conjugating organometallic moieties with organic fragments for enhanced efficacy

[Display omitted] In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometa...

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Published inBioorganic chemistry Vol. 149; p. 107510
Main Authors Aqilah Zahirah Norazmi, Nur, Hafizah Mukhtar, Nur, Ravindar, Lekkala, Suhaily Saaidin, Aimi, Huda Abd Karim, Nurul, Hamizah Ali, Amatul, Kartini Agustar, Hani, Ismail, Norzila, Yee Ling, Lau, Ebihara, Masahiro, Izzaty Hassan, Nurul
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.2024
Subjects
Animals
Antimalarial
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Conjugation
Humans
Malaria - drug therapy
Molecular hybridization
Molecular Structure
Organometallic
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Parasitic Sensitivity Tests
Plasmodium falciparum - drug effects
Structure-Activity Relationship
Transition metal
Molecular hybridization
Antimalarial
PQ
ARS
INH
ART
SAR
CHO
FQ
Fc
QN
WHO
LSG
CQS
CQDP
CQR
TSCs
Organometallic
Transition metal
SERM
CP
CQ
ECM
DHODH
HEK
AQ
ACT
MMV
PGM
ROS
CORM
PfCRT
Conjugation
ARM
DHA
PTA
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Abstract [Display omitted] In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine–ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety’s class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.
AbstractList In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.
In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine-ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety's class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.
[Display omitted] In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into biologically active scaffolds has been hailed as an appealing strategy in medicinal chemistry. The conjugation to organometallic fragments can be achieved by an appropriate linker or by directly coordinating the existing drugs to a metal. The success of Ferroquine (FQ, SR97193), an effective chloroquine–ferrocene conjugate currently undergoing the patient-exploratory phase as a combination therapy with the novel triaminopyrimidine ZY-19489 for malaria, has sparked intense interest in organometallic compound drug discovery. We present the evolution of organometallic antimalarial agents over the last decade, focusing on the parent moiety’s class and the type of organometallics involved. Four main organometallic antimalarial compounds have been chosen based on conjugated organic moieties: existing antimalarial drugs, other clinical drugs, hybrid drugs, and promising scaffolds of thiosemicarbazones, benzimidazoles, and chalcones, in particular. The presented insights contribute to the ongoing discourse on organometallic compound drug development for malaria diseases.
ArticleNumber 107510
Author Huda Abd Karim, Nurul
Hamizah Ali, Amatul
Kartini Agustar, Hani
Izzaty Hassan, Nurul
Ebihara, Masahiro
Ravindar, Lekkala
Suhaily Saaidin, Aimi
Yee Ling, Lau
Hafizah Mukhtar, Nur
Aqilah Zahirah Norazmi, Nur
Ismail, Norzila
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  surname: Aqilah Zahirah Norazmi
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  givenname: Nur
  surname: Hafizah Mukhtar
  fullname: Hafizah Mukhtar, Nur
  organization: Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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  givenname: Lekkala
  surname: Ravindar
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  organization: Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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  givenname: Nurul
  surname: Huda Abd Karim
  fullname: Huda Abd Karim, Nurul
  organization: Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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  givenname: Amatul
  surname: Hamizah Ali
  fullname: Hamizah Ali, Amatul
  organization: Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
– sequence: 7
  givenname: Hani
  surname: Kartini Agustar
  fullname: Kartini Agustar, Hani
  organization: Department of Earth Sciences and Environment, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia
– sequence: 8
  givenname: Norzila
  surname: Ismail
  fullname: Ismail, Norzila
  organization: Department of Pharmacology, School of Medicinal Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
– sequence: 9
  givenname: Lau
  surname: Yee Ling
  fullname: Yee Ling, Lau
  organization: Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
– sequence: 10
  givenname: Masahiro
  surname: Ebihara
  fullname: Ebihara, Masahiro
  organization: Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu City 501-1193, Japan
– sequence: 11
  givenname: Nurul
  surname: Izzaty Hassan
  fullname: Izzaty Hassan, Nurul
  email: drizz@ukm.edu.my
  organization: Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
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Keywords Molecular hybridization
Antimalarial
PQ
ARS
INH
ART
SAR
CHO
FQ
Fc
QN
WHO
LSG
CQS
CQDP
CQR
TSCs
Organometallic
Transition metal
SERM
CP
CQ
ECM
DHODH
HEK
AQ
ACT
MMV
PGM
ROS
CORM
PfCRT
Conjugation
ARM
DHA
PTA
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Snippet [Display omitted] In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of...
In the search for novel ligands with efficacy against various diseases, particularly parasitic diseases, molecular hybridization of organometallic units into...
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SubjectTerms Animals
Antimalarial
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Conjugation
Humans
Malaria - drug therapy
Molecular hybridization
Molecular Structure
Organometallic
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Parasitic Sensitivity Tests
Plasmodium falciparum - drug effects
Structure-Activity Relationship
Transition metal
Title Exploring antimalarial potential: Conjugating organometallic moieties with organic fragments for enhanced efficacy
URI https://dx.doi.org/10.1016/j.bioorg.2024.107510
https://www.ncbi.nlm.nih.gov/pubmed/38833991
https://www.proquest.com/docview/3064921457/abstract/
Volume 149
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