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

• Published in: Bioorganic 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
• Language: English
• 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
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107510

[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.