Oroidin is a bromopyrrole

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

, originally isolated from marine sponges in the genus ''

Agelas ''Agelas'' is a genus of sea sponge in the class Demospongiae. Ecology and distribution Members of this genus are filter feeders. and occur in the West Indies, the Mediterranean Sea, the Red Sea and the Indian Ocean in shallow tropical and subtr ...

.'' Its complex structure leads to wide biological activities, which makes Oroidin a potential drug candidate for various diseases. It also serves as

chemical defense Chemical defense is a life history strategy employed by many organisms to avoid consumption by producing toxic or repellent metabolites or chemical warnings which incite defensive behavioral changes. The production of defensive chemicals occurs in ...

in marine sponges.

Occurrence and properties

Oroidin is a

secondary metabolite Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norm ...

extracted from marine sponges. It belongs to the pyrrole-2-aminoimidazole structural class, which is a family of marine

alkaloids Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar st ...

with many secondary metabolites in marine sponges. These compounds show unique structural complexity and exclusively studied biological activities. Oroidin was first extracted from marine sponge ''

'' in 1971. Studies later found that Oroidin is present in other genera of sponges, such as '' Hymeniacidon'', ''Cymbaxinella'', ''

Axinella ''Axinella'' is a genus of sponges in the family Axinellidae first described in 1862 by Eduard Oscar Schmidt Eduard Oscar Schmidt (21 February 1823, in Torgau – 17 January 1886, in Kappelrodeck) was a German zoologist and phycologist. B ...

.'' The relatively simple structure and lower molecular mass of Oroidin compared to other pyrrole-2-aminoimidazoles makes Oroidin suitable for chemical

optimization Mathematical optimization (alternatively spelled ''optimisation'') or mathematical programming is the selection of a best element, with regard to some criterion, from some set of available alternatives. It is generally divided into two subfi ...

. Researchers have synthesized many Oroidin derivatives to improve the biological activities. Adding additional

side chains In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a l ...

and/or

functional groups 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 ...

gives many possibilities for new natural

derivatives The derivative of a function is the rate of change of the function's output relative to its input value. Derivative may also refer to: In mathematics and economics * Brzozowski derivative in the theory of formal languages * Formal derivative, an ...

. Those derivatives can also arise through

dimerization A dimer () (''wikt:di-, di-'', "two" + ''-mer'', "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, Covalent bond, covalent or Intermolecular force, intermolecular. Dimers also have significant im ...

of the parent Oroidin system. Specifically, the polycyclic property of Oroidin helps build diverse polycyclic natural metabolites. Combinations of pyrrolic building blocks and different

cyclization A cyclic compound (or ring compound) is a term for a compound in the field of chemistry in which one or more series of atoms in the compound is connected to form a ring. Rings may vary in size from three to many atoms, and include examples where al ...

fashions produce these polycyclic derivatives. However, details of the

biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...

of these derivatives still remain unclear.

Biological activities

Oroidin analogues have anticancer,

antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agent ...

, and antibiofilm activities and therefore are a potential drug candidate for

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...

parasitic infections Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...

, and

biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

Cancer

Oroidin analogues have the modified structure of the original. Analogues with increasing number of carbon atoms in the

alkane In organic chemistry, an alkane, or paraffin (a historical trivial name that also has other meanings), is an acyclic saturated hydrocarbon. In other words, an alkane consists of hydrogen and carbon atoms arranged in a tree structure in which ...

component of the molecule show higher

cytotoxicity Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cells ...

than the original molecule towards cancer cells, making the analogs a promising anticancer drug candidate. Oroidin analogues appear to inhibit the growth of

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...

cells the most, but the precise mechanism remains unclear. Oroidin further helps cancer treatment development by inhibiting

multidrug resistance Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...

(MDR) activity. MDR possess resistance to anticancer agents and therefore significantly hinders cancer treatment. Oroidin reverses MDR by interfering the MDR

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

activity without having severe toxicity unlike other compounds. It is thus a potential novel drug lead for MDR with no or little toxicity towards cancer patients.

Parasitic diseases

Oroidin also shows moderate

anti-protozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection. A paraphyletic group, protozoans have little in common with each other. For example, ''Entamoeba histolytica'', a unikont eukaryotic ...

activity against several major parasites. Oroidin kills and/or inhibits the growth of ''

Trypanosoma brucei rhodesiense ''Trypanosoma brucei'' is a species of parasitic kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extrace ...

'' (causes

African sleeping sickness African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species '' Trypanosoma brucei''. Humans are infected by two ty ...

), ''

Trypanosoma cruzi ''Trypanosoma cruzi'' is a species of parasitic euglenoids. Among the protozoa, the trypanosomes characteristically bore tissue in another organism and feed on blood (primarily) and also lymph. This behaviour causes disease or the likelihood of ...

,'' (causes

Chagas disease Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by ''Trypanosoma cruzi''. It is spread mostly by insects in the subfamily ''Triatominae'', known as "kissing bugs". The symptoms change over the cou ...

), ''

Leishmania donovani ''Leishmania donovani'' is a species of intracellular parasites belonging to the genus ''Leishmania'', a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishmani ...

'' (causes

Leishmaniasis Leishmaniasis is a wide array of clinical manifestations caused by parasites of the trypanosome genus ''Leishmania''. It is generally spread through the bite of phlebotomine sandflies, ''Phlebotomus'' and ''Lutzomyia'', and occurs most freq ...

), and ''

Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mosqu ...

'' (causes

Malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

)'','' making it a potential treatment for these diseases.

Bacteria biofilm

Oroidin inhibits bacteria

formation and its analog is a pivotal compound in developing biofilm inhibitors.Bacteria biofilm leads to skin infection and is typically resistant to

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

. Therefore, the antibiofilm activity of Oroidin helps develop effective treatment for biofilm skin infection.

Ecological function

Oroidin defends marine sponges against predation and disease outbreak. The sponges produce and secrete Oroidin (possibility with other secondary metabolites) in response to these ecological threats. In 1996, Oroidin and its

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

product, 4,5-dibromo-1H-pyrrole-2-carboxylic acid, were isolated and identified as the

chemical defenses Chemical defense is a life history strategy employed by many organisms to avoid consumption by producing toxic or repellent metabolites or chemical warnings which incite defensive behavioral changes. The production of defensive chemicals occurs in ...

against fish predators. Later, a study found that Oroidin also regulates

bacterioplankton Bacterioplankton refers to the bacterial component of the plankton that drifts in the water column. The name comes from the Ancient Greek word ' ('), meaning "wanderer" or "drifter", and ', a Latin term coined in the 19th century by Christian G ...

communities and inhibit

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

. A study suggests site-specific variation in secretion concentration of Oroidin. This could be due to different environmental conditions, such as differences in ocean depth and

particulate organic matter Particulate organic matter (POM) is a fraction of total organic matter operationally defined as that which does not pass through a filter pore size that typically ranges in size from 0.053 to 2 millimeters. Particulate organic carbon (POC) is ...

(POM) availability. POM is a major nutrient source for sponges at depths, and POM availability increases with increasing depth. Deep sea sponges secrete Oroidin three times more than shallow sponges, possibly due to the increased POM availability for energetic surplus. The chemical defense mechanisms still remain unclear since most studies on Oroidin focus on its biological activities. However, molecules responsible for chemical defense appear to be evolutionary conserved and contribute to the success of marine sponges.

References

Antimalarial agents Halogen-containing alkaloids {{alkaloid-stub

Occurrence and properties

Biological activities

Cancer

Parasitic diseases

Bacteria biofilm

Ecological function

See also

References