Oroidin

Last updated
Oroidin
Oroidin.svg
Names
Preferred IUPAC name
N-[(2E)-3-(2-Amino-1H-imidazol-5-yl)prop-2-en-1-yl]-4,5-dibromo-1H-pyrrole-2-carboxamide
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C11H11Br2N5O/c12-7-4-8(18-9(7)13)10(19)15-3-1-2-6-5-16-11(14)17-6/h1-2,4-5,18H,3H2,(H,15,19)(H3,14,16,17)/b2-1+
    Key: QKJAXHBFQSBDAR-OWOJBTEDSA-N
  • InChI=1/C11H11Br2N5O/c12-7-4-8(18-9(7)13)10(19)15-3-1-2-6-5-16-11(14)17-6/h1-2,4-5,18H,3H2,(H,15,19)(H3,14,16,17)/b2-1+
    Key: QKJAXHBFQSBDAR-OWOJBTEDBG
  • C1=C(NC(=C1Br)Br)C(=O)NC/C=C/C2=CNC(=N2)N
Properties
C11H11Br2N5O
Molar mass 389.051 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Oroidin is a bromopyrrole alkaloid, originally isolated from marine sponges in the genus Agelas. [1] [2] [3] It appears to have a wide range of biological activities, which makes Oroidin a potential drug candidate for various diseases. [4] It also serves as chemical defense in marine sponges. [5]

Contents

Occurrence and properties

Oroidin is a secondary metabolite extracted from marine sponges. [5] It belongs to the pyrrole-2-aminoimidazole structural class, which is a family of marine alkaloids with many secondary metabolites in marine sponges. [6] These compounds show unique structural complexity and exclusively studied biological activities. [4]

Oroidin was first extracted from marine sponge Agelas in 1971. [1] [3] [2] Studies later found that Oroidin is present in other genera of sponges, such as Hymeniacidon , Cymbaxinella, Axinella. [7] [8] [4]

The relatively simple structure and lower molecular mass of Oroidin compared to other pyrrole-2-aminoimidazoles makes Oroidin suitable for chemical optimization. [9] Researchers have synthesized many Oroidin derivatives to improve the biological activities. [6] Adding additional side chains and/or functional groups gives many possibilities for new natural derivatives. [9] Those derivatives can also arise through dimerization of the parent Oroidin system. [10] [11] [12] 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. [7] However, details of the biosynthesis of these derivatives still remain unclear. [10]

Biological activities

Oroidin analogues have anticancer, [13] antiparasitic, [4] and antibiofilm [14] activities and therefore are a potential drug candidate for cancers, parasitic infections, and biofilm.

Cancer

Oroidin analogues have the modified structure of the original. [13] 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. [13] Oroidin analogues appear to inhibit the growth of colon cancer cells the most, but the precise mechanism remains unclear. [13]

Oroidin further helps cancer treatment development by inhibiting multidrug resistance (MDR) activity. [8] MDR possess resistance to anticancer agents and therefore significantly hinders cancer treatment. [8] Oroidin reverses MDR by interfering the MDR enzyme activity without having severe toxicity unlike other compounds. [8] 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 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. [4]

Bacteria biofilm

Oroidin inhibits bacteria biofilm formation and its analog is a pivotal compound in developing biofilm inhibitors. [14] Bacteria biofilm leads to skin infection and is typically resistant to antibiotics. [14] Therefore, the antibiofilm activity of Oroidin helps develop effective treatment for biofilm skin infection.

Ecological function

Sea sponge Agelas Elephant-ear-sponge.jpg
Sea sponge Agelas

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. [15] In 1996, Oroidin and its hydrolysis product, 4,5-dibromo-1H-pyrrole-2-carboxylic acid, were isolated and identified as the chemical defenses against fish predators. [5] [8] Later, a study found that Oroidin also regulates bacterioplankton communities and inhibit pathogenesis. [15]

A study suggests site-specific variation in secretion concentration of Oroidin. [15] This could be due to different environmental conditions, such as differences in ocean depth and particulate organic matter (POM) availability. [15] POM is a major nutrient source for sponges at depths, and POM availability increases with increasing depth. [15] Deep sea sponges secrete Oroidin three times more than shallow sponges, possibly due to the increased POM availability for energetic surplus. [15]

The chemical defense mechanisms still remain unclear since most studies on Oroidin focus on its biological activities. [10] However, molecules responsible for chemical defense appear to be evolutionary conserved and contribute to the success of marine sponges. [5]

See also

References

  1. 1 2 Forenza, S.; Minale, L.; Riccio, R.; Fattorusso, E. (1971). "New bromo-pyrrole derivatives from the sponge Agelas oroides" . Journal of the Chemical Society D: Chemical Communications (18): 1129. doi:10.1039/c29710001129. ISSN   0577-6171.
  2. 1 2 Young, Ian S.; Thornton, Paul D.; Thompson, Alison (2010). "Synthesis of natural products containing the pyrrolic ring" . Natural Product Reports. 27 (12): 1801–1839. doi:10.1039/c0np00014k. ISSN   0265-0568. PMID   20936222.
  3. 1 2 Blunt, John W.; Carroll, Anthony R.; Copp, Brent R.; Davis, Rohan A.; Keyzers, Robert A.; Prinsep, Michèle R. (2018-01-25). "Marine natural products". Natural Product Reports. 35 (1): 8–53. doi:10.1039/C7NP00052A. hdl: 10072/381349 . ISSN   1460-4752. PMID   29335692.
  4. 1 2 3 4 5 Forte, Barbara; Malgesini, Beatrice; Piutti, Claudia; Quartieri, Francesca; Scolaro, Alessandra; Papeo, Gianluca (2009-11-27). "A Submarine Journey: The Pyrrole-Imidazole Alkaloids". Marine Drugs. 7 (4): 705–753. doi: 10.3390/md7040705 . ISSN   1660-3397. PMC   2810223 . PMID   20098608.
  5. 1 2 3 4 Chanas, Brian; Pawlik, Joseph R.; Lindel, Thomas; Fenical, William (1997-01-03). "Chemical defense of the Caribbean sponge Agelas clathrodes (Schmidt)" . Journal of Experimental Marine Biology and Ecology. 208 (1): 185–196. doi:10.1016/S0022-0981(96)02653-6. ISSN   0022-0981.
  6. 1 2 Gjorgjieva, Marina; Masic, Lucija Peterlin; Kikelj, Danijel (2018-10-12). "Antibacterial and Antibiofilm Potentials of Marine Pyrrole-2-Aminoimidazole Alkaloids and their Synthetic Analogs" . Mini-Reviews in Medicinal Chemistry. 18 (19): 1640–1658. doi:10.2174/1389557516666160505120157. PMID   27145848. S2CID   21478361.
  7. 1 2 Al Mourabit, Ali; Potier, Pierre (2000-12-14). <237::aid-ejoc237>3.0.co;2-v "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" . European Journal of Organic Chemistry. 2001 (2): 237–243. doi:10.1002/1099-0690(200101)2001:2<237::aid-ejoc237>3.0.co;2-v. ISSN   1434-193X.
  8. 1 2 3 4 5 da Silva, Fernanda R.; Tessis, Ana Claudia; Ferreira, Patricia F.; Rangel, Luciana P.; Garcia-Gomes, Aline S.; Pereira, Fabio R.; Berlinck, Roberto G. S.; Muricy, Guilherme; Ferreira-Pereira, Antonio (2011-01-05). "Oroidin Inhibits the Activity of the Multidrug Resistance Target Pdr5p from Yeast Plasma Membranes" . Journal of Natural Products. 74 (2): 279–282. doi:10.1021/np1006247. ISSN   0163-3864. PMID   21207971.
  9. 1 2 Zidar, Nace; Montalvão, Sofia; Hodnik, Žiga; Nawrot, Dorota A.; Žula, Aleš; Ilaš, Janez; Kikelj, Danijel; Tammela, Päivi; Mašič, Lucija Peterlin (2014-02-14). "Antimicrobial Activity of the Marine Alkaloids, Clathrodin and Oroidin, and Their Synthetic Analogues". Marine Drugs. 12 (2): 940–963. doi: 10.3390/md12020940 . ISSN   1660-3397. PMC   3944524 . PMID   24534840.
  10. 1 2 3 Das, Jayanta; Bhandari, Manojkumar; Lovely, Carl J. (2016-01-01), Atta-ur-Rahman (ed.), Chapter 10 - Isolation, Bioactivity, and Synthesis of Nagelamides , Studies in Natural Products Chemistry, vol. 50, Elsevier, pp. 341–371, doi:10.1016/b978-0-444-63749-9.00010-4, ISBN   9780444637499 , retrieved 2023-04-09
  11. ↑ Stout, E. Paige; Morinaka, Brandon I.; Wang, Yong-Gang; Romo, Daniel; Molinski, Tadeusz F. (2012-04-27). "De Novo Synthesis of Benzosceptrin C and Nagelamide H from 7- 15 N-Oroidin: Implications for Pyrrole–Aminoimidazole Alkaloid Biosynthesis". Journal of Natural Products. 75 (4): 527–530. doi:10.1021/np300051k. ISSN   0163-3864. PMC   3694594 . PMID   22455452.
  12. ↑ Stout, E. Paige; Wang, Yong-Gang; Romo, Daniel; Molinski, Tadeusz F. (2012-05-14). "Pyrrole Aminoimidazole Alkaloid Metabiosynthesis with Marine Sponges Agelas conifera and Stylissa caribica". Angewandte Chemie International Edition. 51 (20): 4877–4881. doi:10.1002/anie.201108119. PMC   3917718 . PMID   22473581.
  13. 1 2 3 4 Dyson, Lauren; Wright, Anthony D.; Young, Kelly A.; Sakoff, Jennette A.; McCluskey, Adam (2014-03-01). "Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin" . Bioorganic & Medicinal Chemistry. 22 (5): 1690–1699. doi:10.1016/j.bmc.2014.01.021. ISSN   0968-0896. PMID   24508308.
  14. 1 2 3 Richards, Justin J.; Reyes, Samuel; Stowe, Sean D.; Tucker, Ashley T.; Ballard, T. Eric; Mathies, Laura D.; Cavanagh, John; Melander, Christian (2009-08-13). "Amide Isosteres of Oroidin: Assessment of Antibiofilm Activity and C. elegans Toxicity". Journal of Medicinal Chemistry. 52 (15): 4582–4585. doi:10.1021/jm900378s. ISSN   0022-2623. PMC   2739084 . PMID   19719234.
  15. 1 2 3 4 5 6 Clayshulte Abraham, A; Gochfeld, DJ; Avula, B; Macartney, KJ; Lesser, MP; Slattery, M (2022-06-02). "Variability in antimicrobial chemical defenses in the Caribbean sponge Agelas tubulata: implications for disease resistance and resilience" . Marine Ecology Progress Series. 690: 51–64. doi:10.3354/meps14042. ISSN   0171-8630.
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