Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Huawei Zhang
 + 1114 word(s) 1114 2021-12-21 07:33:20 |
2 revised
Camila Xu
 + 51 word(s) 1165 2021-12-29 07:18:38 | |
3 revised
Camila Xu
 Meta information modification 1165 2021-12-29 07:19:51 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Zhang, H. Marine-derived 1,3-Oxazole-Containing Alkaloids. Encyclopedia. Available online: https://encyclopedia.pub/entry/17593 (accessed on 27 July 2024).
Zhang H. Marine-derived 1,3-Oxazole-Containing Alkaloids. Encyclopedia. Available at: https://encyclopedia.pub/entry/17593. Accessed July 27, 2024.
Zhang, Huawei. "Marine-derived 1,3-Oxazole-Containing Alkaloids" Encyclopedia, https://encyclopedia.pub/entry/17593 (accessed July 27, 2024).
Zhang, H. (2021, December 28). Marine-derived 1,3-Oxazole-Containing Alkaloids. In Encyclopedia. https://encyclopedia.pub/entry/17593
Zhang, Huawei. "Marine-derived 1,3-Oxazole-Containing Alkaloids." Encyclopedia. Web. 28 December, 2021.
Marine-derived 1,3-Oxazole-Containing Alkaloids
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ph14121274

1,3-Oxazole compounds are a unique class of five-membered monocyclic heteroarenes, containing a nitrogen atom and an oxygen. These alkaloids have attracted extensive attention from medicinal chemists and pharmacologists owing to their diverse arrays of chemical structures and biological activities, and a series of 1,3-oxazole derivatives has been developed into therapeutic agents, such as almoxatone, befloxatone, cabotegravir, delpazolid, fenpipalone, haloxazolam, inavolisib. 

oxazole alkaloid marine natural product bioactive property marine organism marine sponge symbiotic microorganism

1. Peptides

Two novel linear and achiral polyketide-peptides, ariakemicins A (18) and B (19), were obtained as an inseparable mixture from one marine gliding bacterium Rapidithrix sp., collected off the muddy land alongside the Ariake Inland Sea, and displayed selectively antimicrobial activities against Gram-positive bacteria (Brevibacterium sp., S. aureus, and Bacillus subtilis), and weak cytotoxicity against cancer cell lines A549 and BHK [1]. Breitfussins A–H (20–27) were the first marine natural products containing an indole-oxazole-pyrrole framework from hydrozoan Thuiaria breitfussi inhabits in the Arctic ocean, and were found to excellently inhibit PIM1 and DRAK1 kinases [2][3]. Furthermore, breitfussin C (22) strongly exhibited a cytotoxic effect on cancer cell lines (MCF-7, HT-29, MOLT-4, MV-4-11 and MRC-5). One concise total synthesis of the halogen-rich dipeptides 20 and 21 was created by Bayer and his coworkers in 2015, which consists of the palladium-catalyzed cross-coupling of indole and pyrrole on an oxazole core and selective lithiation/iodination of a common indole-oxazole fragment [4]. Mechercharmycin B (28) was a new linear peptide containing four 1,3-oxazole rings produced by the marine strain Thermoactinomyces sp. YM3-251 from Mecherchar (Palau) [5]. Siphonazole (29) and dimethoxy analog (30) were the first naturally occurring substances that incorporated oxazole subunits connected by a two-carbon tether from a marine microbe Herpetosiphon sp., and exhibited selective cytotoxicity to human breast cancer HTB-129 and acute T cell leukemia TIB-152 [6]. The first chemical synthesis of 29 was achieved in 2007 through the preparation of an oxazole ring using rhodium carbene, and the installation of the pentadienyl amino side-chain [7].

2. Macrolides

Two cytotoxic isomers, phorboxazoles A (138) (Scheme 10) and B (139), as well as the precursor (140) were detected in the Indian Ocean marine sponge Phorbas sp. [8][9]. Leiodolides A (141) and B (142) were the first members of a new class of mixed polyketide-nonribosomal peptide synthetase from the deep-water marine sponge Leiodermatium. They structurally possess a 19-membered ring and several unique functional groups, including a bromine substituent and an α-hydroxy-α-methyl carboxylic acid side-chain terminus. These substances had obvious cytotoxic effects against human colon cancer HCT-116 with IC50 values of 2.5 and 5.6 μM, respectively [10]. Chemical investigation of the Madagascan sponge Fascaplysinopsis sp. afforded three macrolides with bis-epoxide motif salarins 143–145, which showed pronounced inhibitory on human leukemia cell lines UT-7 [11][12]. Theonezolides A–C (146–148) from the Okinawan Theonella sp. were novel oxazole-containing macrolides that compose of two main fatty acid chains, including a 37-membered macrolide ring with long side chains connected by amide bonds. They exhibited cytotoxicity on a murine lymphoma L1210 and human epidermoid carcinoma KB cells and induced a platelet morphology change and aggregation in rabbits [13][14][15].

3. Polyketides

By OSMAC (one strain many compounds) strategy, inthomycin B (217) was produced by the marine sediment-derived Streptomyces YB104 and was found to have anti-oomycete, cytotoxic and herbicidal activities [16]. One concise method to synthesize 217 was developed by Webb and coworkers through the Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit and a Kiyooka ketene acetal/amino acid-derived oxazaborolidine procedure as its cornerstones [17]. And the gene cluster (itm) responsible for biosynthesis of 217 was identified as a 95.3 kb trans-AT type I PKS system, of which the gene Itm15 is a cyclodehydrase to catalyze the formation of oxazole ring [16].

By extensive chromatographic techniques, eight hennoxazoles (222–229) were isolated from the sponge Polyfibrospongia sp., of which 222 had peripheral analgesic activity equivalent to the positive control of indomethacin, and 228 exhibited the greatest cytotoxicity toward L1210 with an IC50 value of 2 µg/mL [18][19]. Antibiotic B-90063 (230) was a novel endothelin-converting enzyme (ECE) inhibitor from the marine strain Blastobacter sp. SANK 71894, collected off the coast of Ojika Peninsula [20]. Bengazoles 231–236 were antifungal agents obtained from the marine sponge Pachastrissa sp., collected at Musha Archipelago (Djibouti) [21]. An uncommon oxazole, bengazole A (237) from the sponge Jaspis sp., displayed remarkable ergosterol-dependent antifungal activity against C. albicans, which is equivalent to amphotericin B [22].

4. Benzoxazoles

Chemical study of a halophilic strain Nocardiopsis lucentensis DSM 44048 yielded seven new benzoxazoles, nocarbenzoxazoles A–G (264–270) (Scheme 17), in which 270 had selective activity against HepG2 and HeLa cell lines with a IC50 of 3 and 1 μM, respectively [23]. Recently, a simple route to the synthesis of 269 and 270 was achieved by microwave-assisted construction of a benzoxazole skeleton [24]. One 6-methoxy-2(3H)-benzoxazolinone, coixol (271), was detected in the DCM-MeOH extract of the marine sponge Oceanapia sp., collected off Mandapam coast (India), and had extensive bioactivities, including an inhibitory effect on brine shrimp, anti-inflammation and anti-diabetes [25]. Bioassay-guided fractionation of an extract from the sea plum Pseudopterogorgia elisabethae led to the isolation of homopseudopteroxazole (272), pseudopteroxazole (273), seco-pseudopteroxazole (274) and ileabethoxazole (275) [26][27]. Oxazocurcuphenol (276) was isolated and characterized from the coral P. rigida, collected at Lighthouse Point on the Eleuthera island (Nassau, Bahamas) [28]. Biological tests suggested that 272 and 273–275 strongly inhibited the growth of Mycobacterium tuberculosis H37R0v at 12.5 µg/mL. Compounds 272 and 273 were chemically synthesized by a rapid one-pot method [29], and the total synthesis of 275 was accomplished using a new enantioselective approach [30].
Pharmaceuticals 14 01274 sch017 550
Scheme 17. Marine-derived benzoxazoles (254–285).
To the best of our knowledge, citharoxazole (277) was the first chlorinated oxazole-containing pyrrolo[4,3,2-de]quinoline from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae [31]. Culture of the marine fungus Penicillium sp. from a marine sediment resulted in the production of herqueioxazole (278), which was the first oxazole-containing phenalenone [32].

5. Conclusions

In recent decades, a tremendous number of 1,3-oxazole-containing alkaloids have been isolated and characterized from marine organisms, including marine invertebrates, nematodes, insects, vertebrates cyanobacteria, bacteria, and fungi. These substances possess unique chemical structures and exhibit a wide variety of biological properties. Many important marine-derived 1,3-oxazoles have great potential for the development of leading compounds in the search for new drugs and medicines. For example, mechercharmycin A (119) is a promising antitumor remedy, and (19Z)-halichondramide (168), neohalichondramide (175), and calyculin A–D (190, 200–202) have the potential to treat human leukemia cell line. Besides, plenty of these substances are potential antimicrobial agents, such as kocurin (118), TP-1161 (121) homopseudopteroxazole (272), and so on. However, (1) how to reduce cytotoxicity, (2) how to improve drug stability, and (3) how to make the drug work quickly and effectively in vivo still needs to be studied in further depth.
In recent years, however, the number of new 1,3-oxazole derivatives from marine organisms has greatly decreased, since almost all accessible macroorganisms have been collected and chemically analyzed. Simultaneously, marine microorganisms are shown to be one prolific and unexploited source of bioactive natural products, owing to their species richness and abundant secondary metabolite BGCs, especially symbiotic microbes of marine sponges, seaweeds, mangroves and tunicates [33][34][35][36]. In order to discover novel marine microbe-derived 1,3-oxazoles for new drug discovery, more efforts should be made to conduct strain isolation and chemical study using a combination of classical methods (e.g., cultivation and fermentation, bioassay-guided fractionation, structure elucidation) and advanced analytical techniques (e.g., metabolomics, higher-field NMR instruments, probe technology), genome mining and engineering and microbial cultivating systems (e.g., OSMAC approach) [37].

References

  1. Oku, N.; Adachi, K.; Matsuda, S.; Kasai, H.; Takatsuki, A.; Shizuri, Y. Ariakemicins A and B, novel polyketide-peptide antibi-otics from a marine gliding bacterium of the genus Rapidithrix. Org. Lett. 2008, 10, 2481–2484.
  2. Hansen, K.; Andersen, J.H.; Bayer, A.; Pandey, S.K.; Lorentzen, M.; Jørgensen, K.B.; Sydnes, M.O.; Guttormsen, Y.; Baumann, M.; Koch, U.; et al. Kinase chemodiversity from the arctic: The breitfussins. J. Med. Chem. 2019, 62, 10167–10181.
  3. Hanssen, K.; Schuler, B.; Williams, A.; Demissie, T.B.; Hansen, E.; Andersen, J.H.; Svenson, J.; Blinov, K.; Repisky, M.; Mohn, F.; et al. A combined atomic force microscopy and computational approach for the structural elucidation of breitfussin A and B: highly modified halogenated dipeptides from Thuiaria breitfussi. Angew. Chem. Int. Ed. 2012, 51, 12238–12241.
  4. Pandey, S.K.; Guttormsen, Y.; Haug, B.E.; Hedberg, C.; Bayer, A. A concise total synthesis of breitfussin A and B. Org. Lett. 2014, 17, 122–125.
  5. Kanoh, K.; Matsuo, Y.; Adachi, K.; Imagawa, H.; Nishizawa, M.; Shizuri, Y. Mechercharmycins A and B, cytotoxic substances from marine-derived Thermoactinomyces sp. YM3-251. J. Antibiot. 2005, 58, 289–292.
  6. Zhang, J.; Polishchuk, E.A.; Chen, J.; Ciufolini, M.A. Development of an oxazole conjunctive reagent and application to the total synthesis of siphonazoles. J. Org. Chem. 2009, 74, 9140–9151.
  7. Linder, J.; Moody, C.J. The total synthesis of siphonazole, a structurally unusual bis-oxazole natural product. Chem. Commun. 2007, 1508–1509.
  8. Molinski, T.F. Absolute configuration of phorboxazoles A and B from the marine sponge, Phorbas sp. 2. C43 and complete stereochemistry. Tetrahedron Lett. 1996, 37, 7879–7880.
  9. Dalisay, D.S.; Molinski, T.F. Structure elucidation at the nanomole scale. 2. Hemi-phorboxazole A from Phorbas sp. Org. Lett. 2009, 11, 1967–1970.
  10. Sandler, J.S.; Colin, P.L.; Kelly, M.; Fenical, W. Cytotoxic macrolides from a new species of the deep-water marine sponge Leiodermatium. J. Org. Chem. 2006, 71, 7245–7251.
  11. Bishara, A.; Rudi, A.; Aknin, M.; Neumann, D.; Ben-Califa, N.; Kashman, Y. Salarin C, a new cytotoxic sponge-derived nitrogenous macrolide. Tetrahedron Lett. 2008, 49, 4355–4358.
  12. Bishara, A.; Rudi, A.; Aknin, M.; Neumann, D.; Ben-Califa, N.; Kashman, Y. Salarins D–J, seven new nitrogenous macrolides from the Madagascar sponge Fascaplysinopsis sp. Tetrahedron 2010, 66, 4339–4345.
  13. Kobayashi, J.; Kondo, K.; Ishibashi, M.; Walchli, M.R.; Nakamura, T. Theonezolide A: A novel polyketide natural product from the Okinawan marine sponge Theonella sp. J. Am. Chem. Soc. 1993, 115, 6661–6665.
  14. Kondo, K.; Ishibashi, M.; Kobayashi, J. Isolation and structures of theonezolides B and C from the Okinawan marine sponge Theonella sp. Tetrahedron 1994, 50, 8355–8362.
  15. Rho, M.C.; Park, Y.H.; Sasaki, S.; Ishibashi, M.; Kondo, K.; Kobayashi, J.; Ohizumi, Y. The mode of rabbit platelet shape change and aggregation induced by theonezolide-A, a novel polyketide macrolide, isolated from the Okinawan marine sponge Theonella sp. Can. J. Physiol. Pharmacol. 1996, 74, 193–199.
  16. Hou, S.Y.; Zhang, M.Y.; Wang, H.D.; Zhang, Y.X. Characterization of the biosynthesis gene cluster and oxazole ring formation enzyme for inthomycins in Streptomyces sp. strain SYP-A7193. Appl. Environ. Microbiol. 2020, 86, 1–44.
  17. Webb, M.R.; Donald, C.; Taylor, R.J.K. A general route to the Streptomyces-derived inthomycin family: the first synthesis of (+)-inthomycin B. Tetrahedron Lett. 2006, 47, 549–552.
  18. Higa, T.; Tanaka, J.I.; Kitamura, A.; Koyama, T.; Takahashia, M.; Uchida, T. Bioactive compounds from marine sponges. Pure Appl. Chem. 1994, 66, 2227–2230.
  19. Ichiba, T.; Yoshida, W.Y.; Scheuer, P.J.; Higa, T.; Gravalos, D.G. Hennoxazoles, bioactive bisoxazoles from a marine sponge. J. Am. Chem. Soc. 1991, 113, 3173–3174.
  20. Takaishi, S.; Tuchiya, N.; Sato, A.; Negishi, T.; Takamatsu, Y.; Matsushita, Y.; Watanabe, T.; Iijima, Y.; Haruyama, H.; Kinoshita, T.; et al. B-90063, a novel endothelin converting enzyme inhibitor isolated from a new marine bacterium, Blastobacter sp. SANK 71894. J. Antibiot. 1998, 51, 805–815.
  21. Fernández, R.; Dherbomez, M.; Letourneux, Y.; Nabil, M.; Verbist, A.J.F.; Biard§, J.F. Antifungal metabolites from the marine sponge Pachastrissa sp.: New bengamide and bengazole derivatives. J. Nat. Prod. 1999, 62, 678–680.
  22. Mulder, R.J.; Shafer, C.M.; Dalisay, D.S.; Molinski, T.F. Synthesis and structure–activity relationships of bengazole A analogs. Bioorganic Med. Chem. Lett. 2009, 19, 2928–2930.
  23. Sun, M.; Zhang, X.; Hao, H.; Li, W.; Lu, C. Nocarbenzoxazoles A-G, benzoxazoles produced by halophilic Nocardiopsis lucen-tensis DSM 44048. J. Nat. Prod. 2015, 78, 2123–2127.
  24. Kim, T.; Lee, S.A.; Noh, T.; Choi, P.; Choi, S.J.; Song, B.G.; Kim, Y.; Park, Y.T.; Huh, G.; Kim, Y.J.; et al. Synthesis, structure revision, and cytotoxicity of nocarbenzoxazole G. J. Nat. Prod. 2019, 82, 1325–1330.
  25. Venkateswarlu, Y.; Reddy, N.S.; Ramesh, P.; Rao, J.V. Coixol: A bioactive principle from a marine sponge Oceanapia sp. Biochem. Syst. Ecol. 1999, 27, 519–520.
  26. Rodríguez, I.I.; Rodríguez, A.D. Homopseudopteroxazole, a new antimycobacterial diterpene alkaloid from Pseudopterogorgia elisabethae. J. Nat. Prod. 2003, 66, 855–857.
  27. Rodriguez, A.D.; Ramıirez, C.; Rodriguez, I.I.; Gonzalez, E. Novel antimycobacterial benzoxazole alkaloids, from the west Indian sea whip Pseudopterogorgia elisabethae. Org. Lett. 1999, 1, 527–530.
  28. Georgantea, P.; Ioannou, E.; Evain-Bana, E.; Bagrel, D.; Martinet, N.; Vagias, C.; Roussis, V. Sesquiterpenes with inhibitory activity against CDC25 phosphatases from the soft coral Pseudopterogorgia rigida. Tetrahedron 2016, 72, 3262–3269.
  29. McCulloch, M.W.B.; Berrue, F.; Haltli, B.; Kerr, R.G. One-Pot syntheses of pseudopteroxazoles from pseudopterosins: A rapid route to non-natural congeners with improved antimicrobial activity. J. Nat. Prod. 2011, 74, 2250–2256.
  30. Zhang, X.; Fang, X.; Xu, M.; Lei, Y.; Wu, Z.; Hu, X. Enantioselective total synthesis of pseudopteroxazole and ileabethoxazole. Angew. Chem. Int. Ed. 2019, 58, 7845–7849.
  31. Genta-Jouve, G.; Francezon, N.; Puissant, A.; Auberger, P.; Vacelet, J.; Pérez, T.; Fontana, A.; Al Mourabit, A.; Thomas, O.P. Structure elucidation of the new citharoxazole from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae. Magn. Reson. Chem. 2011, 49, 533–536.
  32. Julianti, E.; Lee, J.H.; Liao, L.; Park, W.; Park, S.; Oh, D.C.; Oh, K.B.; Shin, J. New polyaromatic metabolites from a marine-derived fungus Penicillium sp. Org. Lett. 2013, 15, 1286–1289.
  33. Zhang, H.; Zhao, Z.; Wang, H. Cytotoxic natural products from marine sponge-derived microorganisms. Mar. Drugs 2017, 15, 68.
  34. Kamat, S.; Kumari, M.; Taritla, S.; Jayabaskaran, C. Endophytic fungi of marine alga from Konkan coast, India—A rich source of bioactive material. Front. Mar. Sci. 2020, 7, 1–16.
  35. Chen, S.; Cai, R.; Liu, Z.; Cui, H.; She, Z. Secondary metabolites from mangrove-associated fungi: Source, chemistry and bioactivities. Nat. Prod. Rep. 2021.
  36. Ramesh, C.; Tulasi, B.R.; Raju, M.; Thakur, N.; Dufosse, L. Marine natural products from tunicates and their associated mi-crobes. Mar. Drugs 2021, 19, 308.
  37. Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; the International Natural Product Sciences Taskforce; Supuran, C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov. 2021, 20, 200–216.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Medicine, Research & Experimental
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Huawei Zhang
View Times: 480
Revisions: 3 times (View History)
Update Date: 29 Dec 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback