:Oroidin

Oroidin is a secondary metabolite extracted from marine sponges. It belongs to the pyrrole-2-aminoimidazole structural class, which is a family of marine alkaloids with many secondary metabolites in marine sponges.{{Cite journal |last1=Gjorgjieva |first1=Marina |last2=Masic |first2=Lucija Peterlin |last3=Kikelj |first3=Danijel |date=2018-10-12 |title=Antibacterial and Antibiofilm Potentials of Marine Pyrrole-2-Aminoimidazole Alkaloids and their Synthetic Analogs |url=http://www.eurekaselect.com/141805/article |journal=Mini-Reviews in Medicinal Chemistry |language=en |volume=18 |issue=19 |pages=1640–1658 |doi=10.2174/1389557516666160505120157|pmid=27145848 |s2cid=21478361 |url-access=subscription }} These compounds show unique structural complexity and exclusively studied biological activities.

Oroidin was first extracted from marine sponge Agelas in 1971. Studies later found that Oroidin is present in other genera of sponges, such as Hymeniacidon, Cymbaxinella, Axinella.{{Cite journal |last1=Al Mourabit |first1=Ali |last2=Potier |first2=Pierre |date=2000-12-14 |title=Sponge's Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole: A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau'amine Congeners |url=http://dx.doi.org/10.1002/1099-0690(200101)2001:2<237::aid-ejoc237>3.0.co;2-v |journal=European Journal of Organic Chemistry |volume=2001 |issue=2 |pages=237–243 |doi=10.1002/1099-0690(200101)2001:2<237::aid-ejoc237>3.0.co;2-v |issn=1434-193X|url-access=subscription }}{{Cite journal |last1=da Silva |first1=Fernanda R. |last2=Tessis |first2=Ana Claudia |last3=Ferreira |first3=Patricia F. |last4=Rangel |first4=Luciana P. |last5=Garcia-Gomes |first5=Aline S. |last6=Pereira |first6=Fabio R. |last7=Berlinck |first7=Roberto G. S. |last8=Muricy |first8=Guilherme |last9=Ferreira-Pereira |first9=Antonio |date=2011-01-05 |title=Oroidin Inhibits the Activity of the Multidrug Resistance Target Pdr5p from Yeast Plasma Membranes |url=http://dx.doi.org/10.1021/np1006247 |journal=Journal of Natural Products |volume=74 |issue=2 |pages=279–282 |doi=10.1021/np1006247 |pmid=21207971 |issn=0163-3864|url-access=subscription }}

The relatively simple structure and lower molecular mass of Oroidin compared to other pyrrole-2-aminoimidazoles makes Oroidin suitable for chemical optimization.{{Cite journal |last1=Zidar |first1=Nace |last2=Montalvão |first2=Sofia |last3=Hodnik |first3=Žiga |last4=Nawrot |first4=Dorota A. |last5=Žula |first5=Aleš |last6=Ilaš |first6=Janez |last7=Kikelj |first7=Danijel |last8=Tammela |first8=Päivi |last9=Mašič |first9=Lucija Peterlin |date=2014-02-14 |title=Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues |journal=Marine Drugs |language=en |volume=12 |issue=2 |pages=940–963 |doi=10.3390/md12020940 |issn=1660-3397 |pmc=3944524 |pmid=24534840 |doi-access=free }} Researchers have synthesized many Oroidin derivatives to improve the biological activities. Adding additional side chains and/or functional groups gives many possibilities for new natural derivatives. Those derivatives can also arise through dimerization of the parent Oroidin system.{{Citation |last1=Das |first1=Jayanta |title=Chapter 10 - Isolation, Bioactivity, and Synthesis of Nagelamides |date=2016-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780444637499000104 |volume=50 |pages=341–371 |editor-last=Atta-ur-Rahman |access-date=2023-04-09 |publisher=Elsevier |language=en |doi=10.1016/b978-0-444-63749-9.00010-4 |last2=Bhandari |first2=Manojkumar |last3=Lovely |first3=Carl J.|series=Studies in Natural Products Chemistry |isbn=9780444637499 |url-access=subscription }}{{Cite journal |last1=Stout |first1=E. Paige |last2=Morinaka |first2=Brandon I. |last3=Wang |first3=Yong-Gang |last4=Romo |first4=Daniel |last5=Molinski |first5=Tadeusz F. |date=2012-04-27 |title=De Novo Synthesis of Benzosceptrin C and Nagelamide H from 7- 15 N-Oroidin: Implications for Pyrrole–Aminoimidazole Alkaloid Biosynthesis |journal=Journal of Natural Products |language=en |volume=75 |issue=4 |pages=527–530 |doi=10.1021/np300051k |issn=0163-3864 |pmc=3694594 |pmid=22455452}}{{Cite journal |last1=Stout |first1=E. Paige |last2=Wang |first2=Yong-Gang |last3=Romo |first3=Daniel |last4=Molinski |first4=Tadeusz F. |date=2012-05-14 |title=Pyrrole Aminoimidazole Alkaloid Metabiosynthesis with Marine Sponges Agelas conifera and Stylissa caribica |journal=Angewandte Chemie International Edition |language=en |volume=51 |issue=20 |pages=4877–4881 |doi=10.1002/anie.201108119 |pmc=3917718 |pmid=22473581}} Specifically, the polycyclic property of Oroidin helps build diverse polycyclic natural metabolites. Combinations of pyrrolic building blocks and different cyclization dimerization fashions produce these polycyclic derivatives. However, details of the biosynthesis of these derivatives still remain unclear.

Oroidin analogues have anticancer,{{Cite journal |last1=Dyson |first1=Lauren |last2=Wright |first2=Anthony D. |last3=Young |first3=Kelly A. |last4=Sakoff |first4=Jennette A. |last5=McCluskey |first5=Adam |date=2014-03-01 |title=Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin |url=https://www.sciencedirect.com/science/article/pii/S0968089614000492 |journal=Bioorganic & Medicinal Chemistry |language=en |volume=22 |issue=5 |pages=1690–1699 |doi=10.1016/j.bmc.2014.01.021 |pmid=24508308 |issn=0968-0896|url-access=subscription }} antiparasitic, and antibiofilm{{Cite journal |last1=Richards |first1=Justin J. |last2=Reyes |first2=Samuel |last3=Stowe |first3=Sean D. |last4=Tucker |first4=Ashley T. |last5=Ballard |first5=T. Eric |last6=Mathies |first6=Laura D. |last7=Cavanagh |first7=John |last8=Melander |first8=Christian |date=2009-08-13 |title=Amide Isosteres of Oroidin: Assessment of Antibiofilm Activity and C. elegans Toxicity |journal=Journal of Medicinal Chemistry |language=en |volume=52 |issue=15 |pages=4582–4585 |doi=10.1021/jm900378s |issn=0022-2623 |pmc=2739084 |pmid=19719234}} activities and therefore are a potential drug candidate for cancers, parasitic infections, and biofilm.

Oroidin analogues have the modified structure of the original. Analogues with increasing number of carbon atoms in the alkane component of the molecule show higher cytotoxicity 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 cells the most, but the precise mechanism remains unclear.

Oroidin further helps cancer treatment development by inhibiting multidrug resistance (MDR) activity. MDR possess resistance to anticancer agents and therefore significantly hinders cancer treatment. Oroidin reverses MDR by interfering the MDR enzyme 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.

Oroidin also shows moderate anti-protozoal activity against several major parasites. Oroidin kills and/or inhibits the growth of Trypanosoma brucei rhodesiense (causes African sleeping sickness), Trypanosoma cruzi, (causes Chagas disease), Leishmania donovani (causes Leishmaniasis), and Plasmodium falciparum (causes Malaria), making it a potential treatment for these diseases.

Oroidin inhibits bacteria biofilm formation and its analog is a pivotal compound in developing biofilm inhibitors.Bacteria biofilm leads to skin infection and is typically resistant to antibiotics. Therefore, the antibiofilm activity of Oroidin helps develop effective treatment for biofilm skin infection.

File:Elephant-ear-sponge.jpg]]

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.{{Cite journal |last1=Clayshulte Abraham |first1=A |last2=Gochfeld |first2=DJ |last3=Avula |first3=B |last4=Macartney |first4=KJ |last5=Lesser |first5=MP |last6=Slattery |first6=M |date=2022-06-02 |title=Variability in antimicrobial chemical defenses in the Caribbean sponge Agelas tubulata: implications for disease resistance and resilience |url=http://dx.doi.org/10.3354/meps14042 |journal=Marine Ecology Progress Series |volume=690 |pages=51–64 |doi=10.3354/meps14042 |issn=0171-8630|url-access=subscription }} In 1996, Oroidin and its hydrolysis product, 4,5-dibromo-1H-pyrrole-2-carboxylic acid, were isolated and identified as the chemical defensesagainst fish predators. Later, a study found that Oroidin also regulates bacterioplankton communities and inhibit pathogenesis.

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 (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.

• Alkaloid
• Natural products

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Category:Antimalarial agents

Category:Halogen-containing alkaloids

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