Ferroquine (Ferrochloroquine)
(Synonyms: 二茂铁氯喹; Ferrochloroquine; SSR97193) 目录号 : GC32125Ferroquine (Ferrochloroquine) (Ferrochloroquine) 是 Chloroquine 的二茂铁类似物,是一种抗疟药。
Cas No.:185055-67-8
Sample solution is provided at 25 µL, 10mM.
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Cell experiment: | Cytotoxicity studies are performed on human cervix HeLa cancer cells and non tumorigenic human fetal lung fibroblasts MRC-5 to compare the activity of Ferroquine, RQ, FQ-OH, CQ, MQ and Cisplatin. The cell viability is determined via a colorimetric cell-based assay using Resazurin. Briefly, one day before treatment cells are plated in triplicates in 96-well plates at a density of 4 × 103 cells/well in 100 µL. Upon treating cells with increasing concentrations of the target complexes (freshly prepared stock solution in DMSO), cells are incubated at 37°C/6% CO2 for 48 h, the medium is removed, and 100 µL of complete medium containing resazurin (0.2 mg/mL final concentration) is added. After 4 h of incubation at 37°C/6% CO2, the fluorescence of the highly red fluorescent resorufin product is quantified at 590 nm emission with 540 nm excitation wavelength in a SpectraMax M5 microplate Reader[1]. |
Animal experiment: | Mice[1] Groups of 3-4 NMRI mice are treated orally with single oral doses of 200 mg/kg of Ferroquine, FQ-OH and RQ. In addition, one group of mice is treated with a single oral dose of 800 mg/kg Ferroquine. Untreated mice serve as controls in all experiments. At 21 d post-treatment, animals are killed by the CO2 method and dissected. Worms are removed by picking, then sexed and counted. |
References: [1]. Keiser J, et al. In vitro and in vivo antischistosomal activity of ferroquine derivatives. Parasit Vectors. 2014 Sep 4;7:424. |
Ferroquine is an ingenious antimalarial agent.
The 24 hours post-incubation all newly transformed schistosomula (NTS) exposed to 33.3 µM Ferroquine (FQ), hydroxyl-ferroquine (FQ-OH) and Ruthenoquine (RQ) shows strongly reduced viabilities. 72 hours post-incubation all NTS exposed to 33.3 µM RQ have died, while Ferroquine and FQ-OH treated worms are strongly affected but still alive[1].
Treatment of mice with 200 and 800 mg/kg Ferroquine, shows low total worm burden reductions of 19.4% and 35.6%. One of the mice treated with 800 mg/kg Ferroquine died within 24 hours post-treatment. No activity is observed treating mice with RQ at 200 mg/kg. Finally, a total worm burden reduction of 17.3% is observed following treatment with FQ-OH. Hence, modification of Chloroquine (CQ) by a ferrocenyl or ruthenocenyl fragment does not increase the antischistosomal properties of CQ. For comparison, at 200 mg/kg mefloquine (MQ) achieves a much higher worm burden reduction of 72.3% in S. mansoni-infected mice. A higher effect against female adult S. mansoni is also observed in MQ treated mice pointing to a sex-specific interference of these drugs with the target. Furthermore, in one of the FQ-OH treated mice many dead worms are recovered and a hepatic shift (i.e. worms migrating to the liver) observed. Hence, Ferroquine and FQ-OH show weak antischistosomal activity in vivo[1].
[1]. Keiser J, et al. In vitro and in vivo antischistosomal activity of ferroquine derivatives. Parasit Vectors. 2014 Sep 4;7:424.
Cas No. | 185055-67-8 | SDF | |
别名 | 二茂铁氯喹; Ferrochloroquine; SSR97193 | ||
Canonical SMILES | ClC1=CC=C2C(NC[C-]34[Fe+2]56789%10%11([CH-]%12[CH]8=[CH]9[CH]%10=[CH]%11%12)C3(CN(C)C)=[CH]5[CH]6=[CH]47)=CC=NC2=C1 | ||
分子式 | C23H24ClFeN3 | 分子量 | 433.75 |
溶解度 | DMSO : 8.33 mg/mL (19.20 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.3055 mL | 11.5274 mL | 23.0548 mL |
5 mM | 0.4611 mL | 2.3055 mL | 4.611 mL |
10 mM | 0.2305 mL | 1.1527 mL | 2.3055 mL |
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A Phase II pilot trial to evaluate safety and efficacy of Ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study
Malar J 2016 Sep 13;15(1):469.PMID:27624471DOI:PMC5022189
Background: Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers. Methods: Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg Ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of Ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study. Results: Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg Ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for Ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although Ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects that may have played a role in the elevated transaminases levels. No clinically significant ECG abnormalities were observed. Conclusions: The parameters and PK/PD model derived from this study pave the way to the further rational development of Ferroquine as an anti-malarial partner drug. The safety of Ferroquine has to be further explored in controlled human trials. Trial registration anzctr.org.au (registration number: ACTRN12613001040752), registered 18/09/2013.