Ferroquine Explained

Ferroquine is a synthetic compound related to chloroquine which acts as an antimalarial, and shows good activity against chloroquine-resistant strains.^[1] It contains an organometallic ferrocene ring which is unusual in pharmaceuticals,^{[2] [3] [4]} and while it was first reported in 1997,^[5] it has progressed slowly through clinical trials, with results from Phase II trials showing reasonable safety and efficacy, and further trials ongoing.^{[6] [7]}

Notes and References

1. Domarle O, Blampain G, Agnaniet H, Nzadiyabi T, Lebibi J, Brocard J, Maciejewski L, Biot C, Georges AJ, Millet P . 6 . In vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine . Antimicrobial Agents and Chemotherapy . 42 . 3 . 540–544 . March 1998 . 9517929 . 10.1128/AAC.42.3.540 . 105495 .
2. Dive D, Biot C . Ferrocene conjugates of chloroquine and other antimalarials: the development of ferroquine, a new antimalarial . ChemMedChem . 3 . 3 . 383–391 . March 2008 . 17806092 . 10.1002/cmdc.200700127 . 7162372 .
3. Biot C, Nosten F, Fraisse L, Ter-Minassian D, Khalife J, Dive D . The antimalarial ferroquine: from bench to clinic . Parasite . 18 . 3 . 207–214 . August 2011 . 21894260 . 10.1051/parasite/2011183207 . 3671469 .
4. Wani WA, Jameel E, Baig U, Mumtazuddin S, Hun LT . Ferroquine and its derivatives: new generation of antimalarial agents . European Journal of Medicinal Chemistry . 101 . 534–551 . August 2015 . 26188909 . 10.1016/j.ejmech.2015.07.009 . 7115395 .
5. Biot C, Glorian G, Maciejewski LA, Brocard JS . Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue . Journal of Medicinal Chemistry . 40 . 23 . 3715–3718 . November 1997 . 9371235 . 10.1021/jm970401y .
6. Held J, Supan C, Salazar CL, Tinto H, Bonkian LN, Nahum A, Moulero B, Sié A, Coulibaly B, Sirima SB, Siribie M, Otsyula N, Otieno L, Abdallah AM, Kimutai R, Bouyou-Akotet M, Kombila M, Koiwai K, Cantalloube C, Din-Bell C, Djeriou E, Waitumbi J, Mordmüller B, Ter-Minassian D, Lell B, Kremsner PG . 6 . Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study . The Lancet. Infectious Diseases . 15 . 12 . 1409–1419 . December 2015 . 26342427 . 10.1016/S1473-3099(15)00079-1 .
7. Adoke Y, Zoleko-Manego R, Ouoba S, Tiono AB, Kaguthi G, Bonzela JE, Duong TT, Nahum A, Bouyou-Akotet M, Ogutu B, Ouedraogo A, Macintyre F, Jessel A, Laurijssens B, Cherkaoui-Rbati MH, Cantalloube C, Marrast AC, Bejuit R, White D, Wells TN, Wartha F, Leroy D, Kibuuka A, Mombo-Ngoma G, Ouattara D, Mugenya I, Phuc BQ, Bohissou F, Mawili-Mboumba DP, Olewe F, Soulama I, Tinto H . 6 . A randomized, double-blind, phase 2b study to investigate the efficacy, safety, tolerability and pharmacokinetics of a single-dose regimen of ferroquine with artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria . Malaria Journal . 20 . 1 . 222 . May 2021 . 34011358 . 10.1186/s12936-021-03749-4 . 8135182 . free .