Buparvaquone

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Buparvaquone
Structure of buparvaquone.png
Clinical data
ATCvet code
Identifiers
  • 2-((4-tert-butylcyclohexyl)methyl)-3-hydroxy-1,4-naphthoquinone
CAS Number
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.115.556 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H26O3
Molar mass 326.436 g·mol−1
3D model (JSmol)
  • CC(C)(C)C3CCC(C\C2=C(/O)C(=O)c1ccccc1C2=O)CC3
  • InChI=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 Yes check.svgY
  • Key:KLLIVCPQDTYMLC-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 ] It is the only really effective commercial therapeutic product against bovine theileriosis, where it has been used since the late 1980s.[ citation needed ]

Contents

Industrial production

It was first produced in Great Britain, then in Germany.[ citation needed ] Its patent expired in the mid-2000s, and was then produced in different countries, e.g., India and Iran.[ citation needed ]

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. [1]

Molecular target

Buparvaquone resistance appears to be associated with parasite mutations in the Qo quinone-binding site of mitochondrial cytochrome b. [2] 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.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Coenzyme Q – cytochrome c reductase</span> Class of enzymes

The coenzyme Q : cytochrome c – oxidoreductase, sometimes called the cytochrome bc1 complex, and at other times complex III, is the third complex in the electron transport chain, playing a critical role in biochemical generation of ATP. Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial and the nuclear genomes. Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders. The bc1 complex contains 11 subunits, 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, and profit. Fungicides are used both in agriculture and to fight fungal infections in animals. Chemicals used to control oomycetes, which are not fungi, are also referred to as fungicides, as oomycetes use the same mechanisms as fungi to infect plants. Fungicides can either be contact, translaminar or systemic. Contact fungicides are not taken up into the plant tissue and protect only the plant where the spray is deposited. Translaminar fungicides redistribute the fungicide from the upper, sprayed leaf surface to the lower, unsprayed surface. Systemic fungicides are taken up and redistributed through the xylem vessels. Few fungicides move to all parts of a plant. Some are locally systemic, and some move upwardly.

<span class="mw-page-title-main">Proguanil</span> Chemical compound

Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistant malaria. It is taken by mouth.

<span class="mw-page-title-main">Pyrazinamide</span> Medication

Pyrazinamide is a medication used to treat tuberculosis. For active tuberculosis, it is often used with rifampicin, isoniazid, and either streptomycin or ethambutol. It is not generally recommended for the treatment of latent tuberculosis. It is taken by mouth.

<span class="mw-page-title-main">Atovaquone</span> Antimicrobial and antiprotozoan drug

Atovaquone, sold under the brand name Mepron, is an antimicrobial medication for the prevention and treatment of Pneumocystis jirovecii pneumonia (PCP).

<span class="mw-page-title-main">Q cycle</span>

The Q cycle describes a series of reactions that describe how the sequential oxidation and reduction of the lipophilic electron carrier Coenzyme Q (CoQ) between the ubiquinol and ubiquinone forms, can result in the net movement of protons across a lipid bilayer.

<span class="mw-page-title-main">Cytochrome b</span> Mitochondrial protein involved in the respiratory chain

Cytochrome b within both molecular and cell biology, is a protein found in the mitochondria of eukaryotic cells. It functions as part of the electron transport chain and is the main subunit of transmembrane cytochrome bc1 and b6f complexes.

<span class="mw-page-title-main">Dalfopristin</span> Chemical compound

Dalfopristin is a semi-synthetic streptogramin antibiotic analogue of ostreogyrcin A. The combination quinupristin/dalfopristin was brought to the market by Rhone-Poulenc Rorer Pharmaceuticals in 1999. Synercid is used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium.

<span class="mw-page-title-main">Treprostinil</span> Chemical compound

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2).

<span class="mw-page-title-main">Cytochrome b5 reductase</span> Class of enzymes

Cytochrome-b5 reductase is a NADH-dependent enzyme that converts ferricytochrome from a Fe3+ form to a Fe2+ form. It contains FAD and catalyzes the reaction:

<span class="mw-page-title-main">Cefquinome</span> Chemical compound

Cefquinome is a fourth-generation cephalosporin with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is only used in veterinary applications.

<i>Theileria</i> Genus of single-celled organisms

Theileria is a genus of parasites that belongs to the phylum Apicomplexa, and is closely related to Plasmodium. Two Theileria species, T. annulata and T. parva, are important cattle parasites. T. annulata causes tropical theileriosis and T. parva causes East Coast fever. Theileria species are transmitted by ticks. The genomes of T. orientalis Shintoku, Theileria equi WA, Theileria annulata Ankara and Theileria parva Muguga have been sequenced and published.

<span class="mw-page-title-main">East Coast fever</span> Tick-borne disease of cattle

East Coast fever, also known as theileriosis, is a disease of cattle which occurs in Africa and is caused by the protozoan parasite Theileria parva. The primary vector which spreads T. parva between cattle is a tick, Rhipicephalus appendiculatus. East Coast fever is of major economic importance to livestock farmers in Africa, killing at least one million cattle each year. The disease occurs in Burundi, Democratic Republic of Congo, Kenya, Malawi, Mozambique, Rwanda, South Sudan, Tanzania, Uganda, Zimbabwe, Zambia. In 2003, East Coast fever was introduced to Comoros by cattle imported from Tanzania. It has been eradicated in South Africa.

<span class="mw-page-title-main">Dimethocaine</span> Stimulant

Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of the reward pathway in the brain. However, dimethocaine is a legal cocaine replacement in some countries and is even listed by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category “synthetic cocaine derivatives”. The structure of dimethocaine, being a 4-aminobenzoic acid ester, resembles that of procaine. It is found as a white powder at room temperature.

<span class="mw-page-title-main">Apricitabine</span> Chemical compound

Apricitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI) against HIV. It is structurally related to lamivudine and emtricitabine, and, like these, is an analogue of cytidine.

<span class="mw-page-title-main">Salicylhydroxamic acid</span> An enzyme inhibitor that inhibits urease and thus can treat some infections

Salicylhydroxamic acid is a drug that is a potent and irreversible enzyme inhibitor of the urease enzyme in various bacteria and plants; it is usually used for urinary tract infections. The molecule is similar to urea but is not hydrolyzable by urease; it thus disrupts the bacteria's metabolism through competitive inhibition. It is also a trypanocidal agent. When administered orally, it is metabolized to salicylamide, which exerts analgesic, antipyretic, and anti-inflammatory effects.

Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended for severe or complicated malaria. It is taken by mouth.

<span class="mw-page-title-main">Naphthoquinone</span>

Naphthoquinones constitute a class of organic compounds structurally related to naphthalene. Two isomers are common for the parent naphthoquinones:

<span class="mw-page-title-main">4-Ipomeanol</span> Chemical compound

4-Ipomeanol (4-IPO) is a pulmonary pre-toxin isolated from sweet potatoes infected with the fungus Fusarium solani. One of the 4-IPO metabolites is toxic to the lungs, liver and kidney in humans and animals. This metabolite can covalently bind to proteins, thereby interfering with normal cell processes.

References

  1. Abdou TA, Abou-El-naga TR, Mahmoud MA (2005). "Clinicopathological Studies on Theileria Annulata Infection in Siwa Oasis in Egypt" (PDF). BS. Vet. Med. J. 15 (2): 40–6.
  2. Sharifiyazdi H, Namazi F, Oryan A, Shahriari R, Razavi M (July 2012). "Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure". Veterinary Parasitology. 187 (3–4): 431–5. doi:10.1016/j.vetpar.2012.01.016. PMID   22305656.