Ferroquine and its derivatives: New generation of antimalarial agents

Abstract

Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development.

Group 11 Metal Complexes with Unsymmetrical Bifunctional Ferrocene Ligands

“…These functionalized ferrocene derivatives and their metal complexes represent an important topic of research in many fields such as organic synthesis, catalysis, asymmetric catalysis, materials chemistry, and in medicine as antimalarial or antitumor agents. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In particular, ferrocenyl phosphines have been studied thoroughly, as represented by the well-known 1,1′-bis(diphenylphosphino)ferrocene (dppf ). [1] Some of us have described the formation of several amidephosphines containing ferrocene units, studied their coordination chemistry, [17,18] and also showed that some gold and silver complexes are active as antitumor agents.…”

“On Water” Sustainable Synthesis of 1,5‐Disubstituted Tetrazoles via Ugi‐Azide Reaction through Perturbation of Kosmotropes Using Nacl.

“…The development of parasite resistance to frontline antimalarial drugs such as chloroquine (CQ) (Figure ), antifolates and recently artemisinin (ART), has underscored the importance of developing new drugs and drug targets to treat the disease . The iron based organometallic antimalarial drug Ferroquine (FQ) is extremely active against both CQ‐susceptible and CQ‐resistant P. falciparum . It is now possible to propose a multifactorial mechanism of action of FQ by its ability to inhibit the formation of hemozoin, to generate reactive oxygen species and target lipids.…”

Recent Highlights in Anti‐infective Medicinal Chemistry from South Africa

“…Given the potent in vivo antimalarial activity of chloroquine derived ferroquine ( 68 ), which is currently undergoing clinical trials, coupled to the observations that the selective uptake of polyamines by malaria parasites increases their accumulation within the parasite, Smith and co‐workers devised two polyamine functionalised ferroquine analogues as typified by 69 . Both of these compounds possessed mid‐nanomolar‐range anti‐plasmodial activity, with no chloroquine cross‐resistance.…”