Synonym
Sitamaquine tosylate; Sitamaquine-tosylate; WR-6026; WR6026; WR 6026;
IUPAC/Chemical Name
N1,N1-diethyl-N6-(6-methoxy-4-methylquinolin-8-yl)hexane-1,6-diamine 4-methylbenzenesulfonate
InChi Key
LOBPWLFCZDGYKW-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H33N3O.C7H8O3S/c1-5-24(6-2)14-10-8-7-9-12-22-20-16-18(25-4)15-19-17(3)11-13-23-21(19)20;1-6-2-4-7(5-3-6)11(8,9)10/h11,13,15-16,22H,5-10,12,14H2,1-4H3;2-5H,1H3,(H,8,9,10)
SMILES Code
O=S(O)(C1=CC=C(C=C1)C)=O.COC2=CC3=C(C=CN=C3C(NCCCCCCN(CC)CC)=C2)C
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Sitamaquine is active against L. donovani, L. infantum, L. mexicana, L. braziliensis, and L. tropica (EC50s = 9.5-19.8 µM). It inhibits mitochondrial complex II, also known as succinate dehydrogenase (SDH), in a cell-free assay when used at concentrations ranging from 10 to 200 µM. Sitamaquine increases intracellular levels of ROS and decreases intracellular ATP levels, as well as induces phosphatidylserine externalization, chromatin fragmentation, and depolarization of the mitochondrial membrane potential, markers of apoptosis, in L. donovani promastigotes.
In vitro activity:
Sitamaquine's antileishmanial effect is not linked to its accumulation in acidocalcisomes. Leishmania species and strains exhibited differences in sitamaquine sensitivity and accumulation, but there was no correlation between them. Sitamaquine accumulation correlated with acidotropic probes, acidocalcisome size, and polyphosphate levels. The Leishmania major AP3delta-null mutant could not accumulate sitamaquine, yet both the parental strain and mutants exhibited similar sensitivities to sitamaquine.
Reference: Antimicrob Agents Chemother. 2008 Nov;52(11):4030-6. https://pubmed.ncbi.nlm.nih.gov/18794384/
In vivo activity:
Oral sitamaquine demonstrated efficacy in Indian visceral leishmaniasis and was well tolerated. At Day 180 in the intent-to-treat population, final cure was achieved in 92 of 106 (87%) patients overall and 25 of 31 (81%), 24 of 27 (89%), 23 of 23 (100%), and 20 of 25 (80%) patients at doses of 1.5, 1.75, 2.0, or 2.5 mg kg(-1) day(-1) sitamaquine, respectively.
Reference: Am J Trop Med Hyg. 2005 Dec;73(6):1005-11. https://pubmed.ncbi.nlm.nih.gov/16354802/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
30.0 |
58.17 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
515.71
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Carvalho L, Luque-Ortega JR, López-Martín C, Castanys S, Rivas L, Gamarro F. The 8-aminoquinoline analogue sitamaquine causes oxidative stress in Leishmania donovani promastigotes by targeting succinate dehydrogenase. Antimicrob Agents Chemother. 2011 Sep;55(9):4204-10. doi: 10.1128/AAC.00520-11. Epub 2011 Jun 13. PMID: 21670183; PMCID: PMC3165367.
2. López-Martín C, Pérez-Victoria JM, Carvalho L, Castanys S, Gamarro F. Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomes. Antimicrob Agents Chemother. 2008 Nov;52(11):4030-6. doi: 10.1128/AAC.00964-08. Epub 2008 Sep 15. PMID: 18794384; PMCID: PMC2573096.
3. Jha TK, Sundar S, Thakur CP, Felton JM, Sabin AJ, Horton J. A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. Am J Trop Med Hyg. 2005 Dec;73(6):1005-11. PMID: 16354802.
4. Mbui J, Rashid R, Lodenyo H, Nyakundi P, Kipmutai R, Mutuma G, Kirigi G, Kinoti D, Wasunna M. Visceral leishmaniasis with concomittant post kala-azar dermal leishmaniasis responds to oral sitamaquine: case report. East Afr Med J. 2003 Aug;80(8):440-2. doi: 10.4314/eamj.v80i8.8738. PMID: 14601788.
In vitro protocol:
1. Carvalho L, Luque-Ortega JR, López-Martín C, Castanys S, Rivas L, Gamarro F. The 8-aminoquinoline analogue sitamaquine causes oxidative stress in Leishmania donovani promastigotes by targeting succinate dehydrogenase. Antimicrob Agents Chemother. 2011 Sep;55(9):4204-10. doi: 10.1128/AAC.00520-11. Epub 2011 Jun 13. PMID: 21670183; PMCID: PMC3165367.
2. López-Martín C, Pérez-Victoria JM, Carvalho L, Castanys S, Gamarro F. Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomes. Antimicrob Agents Chemother. 2008 Nov;52(11):4030-6. doi: 10.1128/AAC.00964-08. Epub 2008 Sep 15. PMID: 18794384; PMCID: PMC2573096.
In vivo protocol:
1. Jha TK, Sundar S, Thakur CP, Felton JM, Sabin AJ, Horton J. A phase II dose-ranging study of sitamaquine for the treatment of visceral leishmaniasis in India. Am J Trop Med Hyg. 2005 Dec;73(6):1005-11. PMID: 16354802.
2. Mbui J, Rashid R, Lodenyo H, Nyakundi P, Kipmutai R, Mutuma G, Kirigi G, Kinoti D, Wasunna M. Visceral leishmaniasis with concomittant post kala-azar dermal leishmaniasis responds to oral sitamaquine: case report. East Afr Med J. 2003 Aug;80(8):440-2. doi: 10.4314/eamj.v80i8.8738. PMID: 14601788.
1: Kinnamon KE, Steck EA, Loizeaux PS, Hanson WL, Chapman WL Jr, Waits VB. The antileishmanial activity of lepidines. Am J Trop Med Hyg. 1978 Jul;27(4):751-7. doi: 10.4269/ajtmh.1978.27.751. PMID: 686239.
2: Langreth SG, Berman JD, Riordan GP, Lee LS. Fine-structural alterations in Leishmania tropica within human macrophages exposed to antileishmanial drugs in vitro. J Protozool. 1983 Aug;30(3):555-61. doi: 10.1111/j.1550-7408.1983.tb01421.x. PMID: 6315928.
3: Berman JD, Lee LS. Activity of antileishmanial agents against amastigotes in human monocyte-derived macrophages and in mouse peritoneal macrophages. J Parasitol. 1984 Apr;70(2):220-5. PMID: 6088749.
4: Theoharides AD, Chung H, Velazquez H. Metabolism of a potential 8-aminoquinoline antileishmanial drug in rat liver microsomes. Biochem Pharmacol. 1985 Jan 15;34(2):181-8. doi: 10.1016/0006-2952(85)90122-4. PMID: 3917669.
5: Berman JD, Gallalee JV. Semiautomated assessment of in vitro activity of potential antileishmanial drugs. Antimicrob Agents Chemother. 1985 Dec;28(6):723-6. doi: 10.1128/AAC.28.6.723. PMID: 3002244; PMCID: PMC180316.
6: Anders JC, Chung H, Theoharides AD. Methemoglobin formation resulting from administration of candidate 8-aminoquinoline antiparasitic drugs in the dog. Fundam Appl Toxicol. 1988 Feb;10(2):270-5. doi: 10.1016/0272-0590(88)90311-9. PMID: 3356313.
7: White MR, Chapman WL Jr, Hanson WL. Chemotherapy of experimental visceral leishmaniasis in the opossum. J Parasitol. 1989 Feb;75(1):176-8. PMID: 2918440.
8: Taylor T, Hawkins DR, Morris GR, Chung H. Pharmacokinetics of the anti- leishmanian agent WR 6026 in dogs. Eur J Drug Metab Pharmacokinet. 1991;Spec No 3:136-9. PMID: 1820868.
9: Vercesi AE, Docampo R. Ca2+ transport by digitonin-permeabilized Leishmania donovani. Effects of Ca2+, pentamidine and WR-6026 on mitochondrial membrane potential in situ. Biochem J. 1992 Jun 1;284 ( Pt 2)(Pt 2):463-7. doi: 10.1042/bj2840463. PMID: 1376113; PMCID: PMC1132661.
10: Idowu OR, Peggins JO, Brewer TG. Side-chain hydroxylation in the metabolism of 8-aminoquinoline antiparasitic agents. Drug Metab Dispos. 1995 Jan;23(1):18-27. PMID: 7720521.
11: Petty BG, Black JR, Hendrix CW, Lewis LD, Basiakos Y, Feinberg J, Pattison DG, Hafner R. Escalating multiple-dose safety and tolerance study of oral WR 6026 in HIV-infected subjects: AIDS clinical trials group 173. J Acquir Immune Defic Syndr. 1999 May 1;21(1):26-32. doi: 10.1097/00126334-199905010-00004. PMID: 10235511.
12: Vercesi AE, Rodrigues CO, Catisti R, Docampo R. Presence of a Na(+)/H(+) exchanger in acidocalcisomes of Leishmania donovani and their alkalization by anti-leishmanial drugs. FEBS Lett. 2000 May 12;473(2):203-6. doi: 10.1016/s0014-5793(00)01531-3. PMID: 10812075.
13: Yeates C. Sitamaquine (GlaxoSmithKline/Walter Reed Army Institute). Curr Opin Investig Drugs. 2002 Oct;3(10):1446-52. PMID: 12431016.
14: Sangraula H, Sharma KK, Rijal S, Dwivedi S, Koirala S. Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. J Assoc Physicians India. 2003 Jul;51:686-90. PMID: 14621038.
