title: 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.
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310, UTM, Skudai, Johor Bahru, Malaysia. Electronic address: waseemorg@gmail.com.
authors.forename: Waseem A
authors.initials: WA
authors.lastname: Wani
authors.affiliation: University Department of Chemistry, B. R. Ambedkar Bihar University, Muzaffarpur, 842001, Bihar, India.
authors.forename: Ehtesham
authors.initials: E
authors.lastname: Jameel
authors.affiliation: Center of Excellence for Scientific Research Collaboration with MIT, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
authors.forename: Umair
authors.initials: U
authors.lastname: Baig
authors.affiliation: University Department of Chemistry, B. R. Ambedkar Bihar University, Muzaffarpur, 842001, Bihar, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Mumtazuddin
authors.affiliation: Institute of Bioproduct Development, Universiti Teknologi Malaysia, 81310, UTM, Skudai, Johor Bahru, Malaysia. Electronic address: lee@ibd.utm.my.
authors.forename: Lee Ting
authors.initials: LT
authors.lastname: Hun
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D000075163:Metallocenes; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; C479230:ferroquine
keywords: Chloroquine-bridged ferrocenophanes; Ferrocene dual conjugates; Ferroquine; Ferroquine derivatives; Future perspectives; Hydroxyferroquines