[
]
Pregnancy and breastfeeding
It is unknown whether it is safe for the baby when a woman takes it while breastfeeding.[
]
Adverse reactions
The most frequent adverse reactions are nausea, vomiting, diarrhea, abdominal pain, and a feeling of general discomfort. It is also common to experience various sensations in the skin, from crawling or tingling sensations, tenderness of palms and the soles, and numbness of hands, arm, legs or feet.[ Other skin reactions include skin rash, swelling and stinging sensation.] Suramin can also cause loss of appetite and irritability.[ Suramin causes non-harmful changes in urine during use, specifically making the urine cloudy.][ It may exacerbate ]kidney disease
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
.[
Less common side effects include extreme fatigue, ulcers in the mouth, and painful tender glands in the neck, armpits and groin.][ Suramin uncommonly affects the eyes causing watery eyes, swelling around the eyes, photophobia, and changes or loss of vision.][
Rare side effects include hypersensitivity reactions causing difficulty breathing. Other rare systemic effects include decreased blood pressure, fever, rapid heart rate, and convulsions.][ Other rare side effects include symptoms of liver dysfunction such as tenderness in upper abdomen, jaundice in eyes and skin, unusual bleeding or bruising.][
Suramin has been applied clinically to HIV/AIDS patients resulting in a significant number of fatal occurrences and as a result the application of this molecule was abandoned for this condition.
]
Pharmacokinetics
Suramin is not orally bioavailable and must be given intravenously. Intramuscular and subcutaneous administration could result in local tissue inflammation or necrosis . Suramin is approximately 99-98% protein bound in the serum and has a half-life of 41–78 days average of 50 days; however, the pharmacokinetics of suramin can vary substantially between individual patients. Suramin does not distribute well into cerebral spinal fluid and its concentration in the tissues is equivalently lower than its concentration in the plasma. Suramin is not extensively metabolized and about 80% is eliminated via the kidneys.[
]
Chemistry
The molecular formula of suramin is C51H40N6O23S6. It is a symmetric
Symmetry (from grc, συμμετρία "agreement in dimensions, due proportion, arrangement") in everyday language refers to a sense of harmonious and beautiful proportion and balance. In mathematics, "symmetry" has a more precise definiti ...
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
in the center of which lies a urea
Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid.
Urea serves an important r ...
(NH–CO–NH) functional group. Suramin contains six aromatic systems – four benzene ring
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
s, sandwiched by a pair of naphthalene
Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromati ...
moieties – plus four amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
s (in addition to the urea) and six sulfonic acid
In organic chemistry, sulfonic acid (or sulphonic acid) refers to a member of the class of organosulfur compounds with the general formula , where R is an organic alkyl or aryl group and the group a sulfonyl hydroxide. As a substituent, it is kn ...
groups. When given as a medication, it is usually delivered as the sodium sulfonate
In organosulfur chemistry, a sulfonate is a salt or ester of a sulfonic acid. It contains the functional group , where R is an organic group. Sulfonates are the conjugate bases of sulfonic acids. Sulfonates are generally stable in water, non-o ...
salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
as this formulation is water-soluble, though it does deteriorate rapidly in air.
The synthesis
Synthesis or synthesize may refer to:
Science Chemistry and biochemistry
*Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors
** Organic synthesis, the chemical synthesis of organ ...
of suramin itself and structural analog
A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a ce ...
s is by successive formation of the amide bonds from their corresponding amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
(aniline
Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine
In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
) and carboxyl
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
(as acyl chloride
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...
) components. Various routes to these compounds have been developed, including starting from separate naphthalene structures and building towards an eventual unification by formation of the urea or starting with a urea and appending successive groups.
Mechanism of action
The mechanism of action for suramin is unclear, but it is thought that parasites are able to selectively uptake suramin via receptor-mediated endocytosis of drug that is bound to low-density lipoproteins and, to a lesser extent, other serum proteins.[ Once inside parasites, suramin combines with proteins, especially trypanosomal ]glycolytic
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
enzymes, to inhibit energy metabolism.
History
Suramin was first made by the chemists Oskar Dressel, Richard Kothe and Bernhard Heymann at Bayer AG
Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutica ...
laboratories in Elberfeld
Elberfeld is a municipal subdivision of the German city of Wuppertal; it was an independent town until 1929.
History
The first official mentioning of the geographic area on the banks of today's Wupper River as "''elverfelde''" was in a docu ...
, after research on a series of urea-like compounds. The drug is still sold by Bayer under the brand name
A brand is a name, term, design, symbol or any other feature that distinguishes one seller's good or service from those of other sellers. Brands are used in business, marketing, and advertising for recognition and, importantly, to create an ...
Germanin. The chemical structure of suramin was kept secret by Bayer for commercial and strategic reasons, but it was elucidated and published in 1924 by Ernest Fourneau
Ernest Fourneau (4 October 1872 – 5 August 1949) was a French pharmacist graduated in Pharmacy 1898 for the Paris university specialist in medicinal chemical and pharmacology who played a major role in the discovery of synthetic local anesthetic ...
and his team at the Pasteur Institute
The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines f ...
.
Research
It is also used as a research reagent
In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
to inhibit the activation of heterotrimeric G proteins in a variety of GPCR
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin
Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction ...
, the A1 adenosine receptor, the D2 receptor
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, i ...
, the P2 receptor P2 receptor may refer to:
Nucleotides if get released into the extracellular environment can lead to cell death or some other harmful cellular consequences. To avoid harm nucleotides should be neutralized, which is accomplished by P2 receptors. Alm ...
, and ryanodine receptors.
Suramin was studied as a possible treatment for prostate cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
in a clinical trial.
Suramin has been studied in a mouse model of autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
and in a small phase I/II human trial.
References
Further reading
*
External links
*
Suramin sodium
National Cancer Institute
{{Portal bar, Medicine
1916 in science
Anthelmintics
Antiprotozoal agents
Bayer brands
Benzanilides
Naphthalenesulfonic acids
Ureas
World Health Organization essential medicines
Wikipedia medicine articles ready to translate