buparvaquone

{{Short description|Chemical compound}}

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{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 459985754

| IUPAC_name = 2-((4-tert-Butylcyclohexyl)methyl)-3-hydroxy-1,4-naphthoquinone

| image = Buparvaquone v2.svg

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 88426-33-9

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| ATCvet = yes

| ATC_prefix = P51

| ATC_suffix = EX03

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| UNII = 0354RT7LG4

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 292009

| chemical_formula =

| C=21 | H=26 | O=3

| smiles = CC(C)(C)C3CCC(C\C2=C(/O)C(=O)c1ccccc1C2=O)CC3

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C21H26O3/c1-21(2,3)14-10-8-13(9-11-14)12-17-18(22)15-6-4-5-7-16(15)19(23)20(17)24/h4-7,13-14,24H,8-12H2,1-3H3

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| StdInChIKey = KLLIVCPQDTYMLC-UHFFFAOYSA-N

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Buparvaquone is a naphthoquinone antiprotozoal drug related to atovaquone. It is a promising compound for the therapy and prophylaxis of all forms of theileriosis. Buparvaquone has been shown to have anti-leishmanial activity in vitro. It can be used to treat bovine East Coast fever protozoa in vitro, along with the only other substance known – Peganum harmala.{{Citation needed|date=February 2010}} It is the only really effective commercial therapeutic product against bovine theileriosis, where it has been used since the late 1980s.{{Citation needed|date=February 2010}}

Industrial production

It was first produced in Great Britain, then in Germany.{{Citation needed|date=February 2010}} Its patent expired in the mid-2000s, and was then produced in different countries such as India and Iran.{{cn|date=December 2022}}

Use in bovine theileriosis

Using a single dose of 2.5 mg/kg, the recovery rate of curable cases is 90 to 98%. In tropical theileriosis, a dosage of 2.0 mg/kg has the same efficacy. Body temperature returns to normal in two to five days.

Parasitemia lowers from 12% on day 0 to 5% the next day, then to 1% by day 5 and none at day 7.{{cite journal | vauthors = Abdou TA, Abou-El-naga TR, Mahmoud MA | title = Clinicopathological Studies on Theileria Annulata Infection in Siwa Oasis in Egypt. | journal = BS. Vet. Med. J. | date = 2005 | volume = 15 | issue = 2 | pages = 40–6 | url = http://old.eaap.org/Previous_Annual_Meetings/2005Uppsala/Papers/M2.11_Abdou.pdf }}

Viruses

Buparvaquone has been shown to inhibit completely vaccinia virus in cell based assay in human cell line.{{Cite journal | vauthors = Witwit H, Cubitt B, Khafaji R, Castro EM, Goicoechea M, Lorenzo MM, Blasco R, Martinez-Sobrido L, de la Torre JC |date=January 2025 |title=Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance |journal=Viruses |language=en |volume=17 |issue=1 |pages=92 |doi=10.3390/v17010092 |doi-access=free |issn=1999-4915|pmc=11769280 }}

Molecular target

Buparvaquone resistance appears to be associated with parasite mutations in the Qo quinone-binding site of mitochondrial cytochrome b.{{cite journal | vauthors = Sharifiyazdi H, Namazi F, Oryan A, Shahriari R, Razavi M | title = Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure | journal = Veterinary Parasitology | volume = 187 | issue = 3–4 | pages = 431–5 | date = July 2012 | pmid = 22305656 | doi = 10.1016/j.vetpar.2012.01.016 }} Its mode of action is thus likely to be similar to that of the antimalarial drug atovaquone, a similar 2-hydroxy-1,4-naphthoquinone that binds to the Qo site of cytochrome b thus inhibiting Coenzyme Q – cytochrome c reductase.{{cn|date=December 2022}}

References