Skip to main content
SpringerLink
Log in

Aplysinopsins as Promising Marine Natural Product Drug Leads: Recent Developments

  • Chapter
  • First Online:
Grand Challenges in Marine Biotechnology

Part of the book series: Grand Challenges in Biology and Biotechnology ((GCBB))

Abstract

Marine natural products represent a rich source of bioactive secondary metabolites, one of which is the marine indole alkaloids aplysinopsins. Aplysinopsins were first described in 1977 from the extracts of Indo-Pacific sponge species. Since that initial description, they have been isolated from a wide range of marine sources: sponges, corals, mollusks, and sea anemones. Aplysinopsins are composed of an indole coupled with an imidazolidinone moiety. The structural variation of naturally occurring aplysinopsin analogs occurs in the bromination pattern on the indole moiety as well as the pattern of N-methylations on the imidazolidinone ring. There are multiple synthetic strategies used to access the aplysinopsin scaffold. The majority of them are convergent routes that begin with synthesis of the desired indole moiety followed by the imidazolidinone synthesis and, ultimately, coupling of the two systems via several different methodologies. Aplysinopsins possess a wide variety of biological activities, from antimicrobial and antimalarial to antitumor activity seen in mice. However, their neuromodulatory activities have generated the most recent interest in their bioactivity. Both natural and synthetic aplysinopsin analogs have been found to act on both the serotonin receptor and the monoamine oxidase system. This chapter will review recently published synthetic strategies used to construct aplysinopsin analogs. It will also highlight significant and promising biological activities displayed by aplysinopsins, with an emphasis of neuromodulatory activities.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Newman DJ, Cragg GM (2016a) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79:629–661. https://doi.org/10.1021/acs.jnatprod.5b01055

    Article  PubMed  CAS  Google Scholar 

  2. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335. https://doi.org/10.1021/np200906s

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Kong D-X, Jiang Y-Y, Zhang H-Y (2010) Marine natural products as sources of novel scaffolds: achievement and concern. Drug Discov Today 15:884–886. https://doi.org/10.1016/j.drudis.2010.09.002

    Article  PubMed  Google Scholar 

  4. Ramirez-Llodra E, Brandt A, Danovaro R, De Mol B, Escobar E, German CR, Levin LA, Martinez Arbizu P, Menot L, Buhl-Mortensen P, Narayanaswamy BE, Smith CR, Tittensor DP, Tyler PA, Vanreusel A, Vecchione M (2010) Deep, diverse and definitely different: unique attributes of the world’s largest ecosystem. Biogeosciences 7:2851–2899. https://doi.org/10.5194/bg-7-2851-2010

    Article  Google Scholar 

  5. Gerwick WH, Moore BS (2012) Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem Biol 19:85–98. https://doi.org/10.1016/j.chembiol.2011.12.014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, Forero-Torres A (2010) Brentuximab Vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363:1812–1821. https://doi.org/10.1056/NEJMoa1002965

    Article  PubMed  CAS  Google Scholar 

  7. Grosso F, Jones RL, Demetri GD, Judson IR, Blay J-Y, Le Cesne A, Sanfilippo R, Casieri P, Collini P, Dileo P, Spreafico C, Stacchiotti S, Tamborini E, Tercero JC, Jimeno J, D’Incalci M, Gronchi A, Fletcher JA, Pilotti S, Casali PG (2007) Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 8:595–602. https://doi.org/10.1016/S1470-2045(07)70175-4

    Article  PubMed  CAS  Google Scholar 

  8. Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ (2011) Cytarabine dose for acute myeloid Leukemia. N Engl J Med 364:1027–1036. https://doi.org/10.1056/NEJMoa1010222

    Article  PubMed  Google Scholar 

  9. Twelves C, Cortes J, Vahdat LT, Wanders J, Akerele C, Kaufman PA (2010) Phase III trials of Eribulin Mesylate (E7389) in extensively Pretreated patients with locally recurrent or metastatic breast cancer. Clin Breast Cancer 10:160–163. https://doi.org/10.3816/CBC.2010.n.023

    Article  PubMed  CAS  Google Scholar 

  10. Schmidtko A, Lötsch J, Freynhagen R, Geisslinger G (2010) Ziconotide for treatment of severe chronic pain. Lancet 375:1569–1577. https://doi.org/10.1016/S0140-6736(10)60354-6

    Article  PubMed  CAS  Google Scholar 

  11. Lee JH, O’Keefe JH, Lavie CJ, Marchioli R, Harris WS (2008) Omega-3 fatty acids for cardioprotection. Mayo Clin Proc 83:324–332. https://doi.org/10.4065/83.3.324

    Article  PubMed  CAS  Google Scholar 

  12. Shepp DH, Dandliker PS, Meyers JD (1986) Treatment of varicella-zoster virus infection in severely immunocompromised patients. A randomized comparison of acyclovir and vidarabine. N Engl J Med 314:208–212. https://doi.org/10.1056/NEJM198601233140404

    Article  PubMed  CAS  Google Scholar 

  13. Newman DJ, Cragg GM (2016b) Drugs and drug candidates from marine sources: an assessment of the current “state of play”. Planta Med 82:775–789. https://doi.org/10.1055/s-0042-101353

    Article  PubMed  CAS  Google Scholar 

  14. Blunt JW, Copp BR, Keyzers RA, Munro MHG, Prinsep MR (2016) Marine natural products. Nat Prod Rep 33:382–431. https://doi.org/10.1039/c5np00156k

    Article  PubMed  CAS  Google Scholar 

  15. Motuhi S-E, Mehiri M, Payri CE, La Barre S, Bach S (2016) Marine natural products from New Caledonia–a review. Mar Drugs 14:58. https://doi.org/10.3390/md14030058

    Article  PubMed Central  CAS  Google Scholar 

  16. Cole AK, Marmura MJ (2010) Triptans: where things stand. Curr Treat Options Neurol 12:454–463. https://doi.org/10.1007/s11940-010-0082-9

    Article  PubMed  Google Scholar 

  17. Kazlauskas R, Murphy PT, Quinn RJ, Wells RJ (1977) Aplysinopsin, a new tryptophan derivative from a sponge. Tetrahedron Lett 18:61–64. https://doi.org/10.1016/S0040-4039(01)92550-X

    Article  Google Scholar 

  18. Fattorusso E, Lanzotti V, Magno S, Novellino E (1985) Tryptophan derivatives from a Mediterranean anthozoan, Astroides calycularis. J Nat Prod 48:924–927. https://doi.org/10.1021/np50042a006

    Article  CAS  Google Scholar 

  19. Okuda RK, Klein D, Kinnel RB, Li M, Scheuer PJ (1982) Marine natural products: the past twenty years and beyond. Pure Appl Chem 54:1907–1914. https://doi.org/10.1351/pac198254101907

    Article  CAS  Google Scholar 

  20. Murata M, Miyagawa-Kohshima K, Nakanishi K, Naya Y (1986) Characterization of compounds that induce symbiosis between sea anemone and anemone fish. Science 234:585–587. https://doi.org/10.1126/science.234.4776.585

    Article  PubMed  CAS  Google Scholar 

  21. Guella G, Mancini I, Zibrowius H, Pietra F (1988) Novel Aplysinopsin-type alkaloids from scleractinian corals of the family Dendrophylliidae of the Mediterranean and the Philippines. Configurational-assignment criteria, stereospecific synthesis, and photoisomerization. Helv Chim Acta 71:773–782. https://doi.org/10.1002/hlca.19880710412

    Article  CAS  Google Scholar 

  22. Guella G, Mancini I, Zibrowius H, Pietra F (1989) Aplysinopsin-type alkaloids from Dendrophyllia sp., a scleractinian coral of the family dendrophylliidae of the Philippines, facile photochemical (Z/E) photoisomerization and thermal reversal. Helv Chim Acta 72:1444–1450. https://doi.org/10.1002/hlca.19890720703

    Article  CAS  Google Scholar 

  23. Johnson JE, Canseco DC, Dolliver DD, Schetz JA, Fronczek FR (2009) Synthesis and characterization of aplysinopsin analogs. J Chem Crystallogr 39:329–336. https://doi.org/10.1007/s10870-008-9480-1

    Article  CAS  Google Scholar 

  24. Segraves NL, Crews P (2005) Investigation of brominated tryptophan alkaloids from two thorectidae sponges: Thorectandra and Smenospongia. J Nat Prod 68:1484–1488. https://doi.org/10.1021/np0501334

    Article  PubMed  CAS  Google Scholar 

  25. Koh E, Sweatman H (2000) Chemical warfare among scleractinians: bioactive natural products from Tubastraea faulkneri Wells kill larvae of potential competitors. J Exp Mar Biol Ecol 251:141–160

    Article  CAS  PubMed  Google Scholar 

  26. Iwagawa T, Miyazaki M, Okamura H, Nakatani M, Doe M, Takemura K (2003) Three novel bis(indole) alkaloids from a stony coral, Tubastraea sp. Tetrahedron Lett 44:2533–2535. https://doi.org/10.1016/S0040-4039(03)00331-9

    Article  CAS  Google Scholar 

  27. Mancini I, Guella G, Zibrowius H, Pietra F (2003) On the origin of quasi-racemic aplysinopsin cycloadducts, (bis)indole alkaloids isolated from scleractinian corals of the family Dendrophylliidae. Involvement of enantiodefective Diels–Alderases or asymmetric induction in artifact processes involving adventitious catalysts? Tetrahedron 59:8757–8762. https://doi.org/10.1016/j.tet.2003.09.038

    Article  CAS  Google Scholar 

  28. Meyer M, Delberghe F, Liron F, Guillaume M, Valentin A, Guyot M (2009) An antiplasmodial new (bis)indole alkaloid from the hard coral Tubastraea sp. Nat Prod Res 23:178–182. https://doi.org/10.1080/14786410801925134

    Article  PubMed  CAS  Google Scholar 

  29. Boyd EM, Sperry J (2010) On the origin of dimeric aplysinopsin alkaloids. Chem N Z 74:109

    CAS  Google Scholar 

  30. Djura P, Faulkner DJ (1980) Metabolites of the marine sponge Dercitus species. J Org Chem 45:735–737. https://doi.org/10.1021/jo01292a043

    Article  CAS  Google Scholar 

  31. Stanovnik B, Svete J (2005) The synthesis Aplysinopsins, Meridianines, and related compounds. Mini-Rev Org Chem 2:211–224. https://doi.org/10.2174/1570193054368864

    Article  CAS  Google Scholar 

  32. Stanovnik B, Jakse R, Groselj U, Sorsak G, Svete J (2007) Synthesis of thioaplysinopsin analogs derived from 5-Dimethylaminomethylidene-2-thioxo-1,3-thiazol-4-ones. Heterocycles 73:743. https://doi.org/10.3987/COM-07-S(U)55

    Article  Google Scholar 

  33. Porwal S, Chauhan SS, Chauhan PMS, Shakya N, Verma A, Gupta S (2009) Discovery of novel antileishmanial agents in an attempt to synthesize pentamidine-aplysinopsin hybrid molecule. J Med Chem 52:5793–5802. https://doi.org/10.1021/jm900564x

    Article  PubMed  CAS  Google Scholar 

  34. Penthala NR, Yerramreddy TR, Crooks PA (2010) Microwave assisted synthesis and in vitro cytotoxicities of substituted (Z)-2-amino-5-(1-benzyl-1H-indol-3-yl)methylene-1-methyl-1H-imidazol-4(5H)-ones against human tumor cell lines. Bioorg Med Chem Lett 20:591–593. https://doi.org/10.1016/j.bmcl.2009.11.083

    Article  PubMed  CAS  Google Scholar 

  35. Penthala NR, Yerramreddy TR, Crooks PA (2011) Synthesis and in vitro screening of novel N-benzyl aplysinopsin analogs as potential anticancer agents. Bioorg Med Chem Lett 21:1411–1413. https://doi.org/10.1016/j.bmcl.2011.01.020

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Thirupathi Reddy Y, Narsimha Reddy P, Koduru S, Damodaran C, Crooks PA (2010) Aplysinopsin analogs: synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones. Bioorg Med Chem 18:3570–3574. https://doi.org/10.1016/j.bmc.2010.03.054

    Article  PubMed  CAS  Google Scholar 

  37. Suzdalev KF, Babakova MN (2016) Synthesis of analogues of Indole alkaloids from sea sponges – Aplysinopsins by the reaction of amines with (4Z)-4-[(1H-indol-3-yl)-methylene]-1,3-oxazol-5(4H)-ones. J Heterocycl Chem 53:1200–1206. https://doi.org/10.1002/jhet.2382

    Article  CAS  Google Scholar 

  38. Hollenbeak KH, Schmitz FJ (1977) Aplysinopsin: antineoplastic tryptophan derivative from the marine sponge Verongia spengelii. Lloydia 40:479–481

    PubMed  CAS  Google Scholar 

  39. Laport MS, Santos OCS, Muricy G (2009) Marine sponges: potential sources of new antimicrobial drugs. Curr Pharm Biotechnol 10:86–105

    Article  CAS  PubMed  Google Scholar 

  40. Gulati D, Chauhan P, Bhakuni R (1994) A new synthesis of aplysinopsin, a marine alkaloid and its analogues and their biological activities. Indian J Chem B 1994:4–9

    Google Scholar 

  41. Tymiak AA, Rinehart KL, Bakus GJ (1985) Constituents of morphologically similar sponges. Tetrahedron 41:1039–1047. https://doi.org/10.1016/S0040-4020(01)96471-3

    Article  CAS  Google Scholar 

  42. Bialonska D, Zjawiony JK (2009) Aplysinopsins – marine Indole alkaloids: chemistry, bioactivity and ecological significance. Mar Drugs 7:166–183. https://doi.org/10.3390/md7020166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Hu J-F, Schetz JA, Kelly M, Peng J-N, Ang KKH, Flotow H, Leong CY, Ng SB, Buss AD, Wilkins SP, Hamann MT (2002) New antiinfective and human 5-HT2 receptor binding natural and semisynthetic compounds from the Jamaican sponge Smenospongia aurea. J Nat Prod 65:476–480

    Article  CAS  PubMed  Google Scholar 

  44. Passemar C, Saléry M, Soh PN, Linas M-D, Ahond A, Poupat C, Benoit-Vical F (2011) Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules. Phytomedicine 18:1118–1125. https://doi.org/10.1016/j.phymed.2011.03.010

    Article  PubMed  CAS  Google Scholar 

  45. WHO|World Malaria Report (2013) [WWW Document], 2013. WHO. http://www.who.int/malaria/publications/world_malaria_report_2013/report/en/. Accessed 26 Feb 2017

  46. Sundar S, Chakravarty J (2010) Antimony toxicity. Int J Environ Res Public Health 7:4267–4277. https://doi.org/10.3390/ijerph7124267

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Poola NR, Kalis M, Plakogiannis FM, Taft DR (2003) Characterization of pentamidine excretion in the isolated perfused rat kidney. J Antimicrob Chemother 52:397–404. https://doi.org/10.1093/jac/dkg341

    Article  PubMed  CAS  Google Scholar 

  48. Bhattacharya SK, Sinha PK, Sundar S, Thakur CP, Jha TK, Pandey K, Das VR, Kumar N, Lal C, Verma N, Singh VP, Ranjan A, Verma RB, Anders G, Sindermann H, Ganguly NK (2007) Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis. J Infect Dis 196:591–598. https://doi.org/10.1086/519690

    Article  PubMed  CAS  Google Scholar 

  49. Cummings DF, Canseco DC, Sheth P, Johnson JE, Schetz JA (2010) Synthesis and structure-affinity relationships of novel small molecule natural product derivatives capable of discriminating between serotonin 5-HT1A, 5-HT2A, 5-HT2C receptor subtypes. Bioorg Med Chem 18:4783–4792. https://doi.org/10.1016/j.bmc.2010.05.017

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Batsanov SS (2001) Van der Waals radii of elements. Inorg Mater 37:871–885. https://doi.org/10.1023/A:1011625728803

    Article  CAS  Google Scholar 

  51. Lewellyn K, Bialonska D, Loria MJ, White SW, Sufka KJ, Zjawiony JK (2013) In vitro structure–activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety–depression model. Bioorg Med Chem 21:7083–7090. https://doi.org/10.1016/j.bmc.2013.09.011

    Article  PubMed  CAS  Google Scholar 

  52. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL (2000) Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102:2836–2841

    Article  CAS  PubMed  Google Scholar 

  53. Centers for Disease Control and Prevention (CDC) (1997) Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb Mortal Wkly Rep 46:1061–1066

    Google Scholar 

  54. Baird-Lambert J, Davis PA, Taylor KM (1982) Methylaplysinopsin: a natural product of marine origin with effects on serotonergic neurotransmission. Clin Exp Pharmacol Physiol 9:203–212. https://doi.org/10.1111/j.1440-1681.1982.tb00798.x

    Article  PubMed  CAS  Google Scholar 

  55. Fiedorowicz JG, Swartz KL (2004) The role of monoamine oxidase inhibitors in current psychiatric practice. J Psychiatr Pract 10:239–248

    Article  PubMed  PubMed Central  Google Scholar 

  56. Youdim MBH, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7:295–309. https://doi.org/10.1038/nrn1883

    Article  PubMed  CAS  Google Scholar 

  57. Prins LHA, Petzer JP, Malan SF (2010) Inhibition of monoamine oxidase by indole and benzofuran derivatives. Eur J Med Chem 45:4458–4466. https://doi.org/10.1016/j.ejmech.2010.07.005

    Article  PubMed  CAS  Google Scholar 

  58. Sant’ Anna Gda S, Machado P, Sauzem PD, Rosa FA, Rubin MA, Ferreira J, Bonacorso HG, Zanatta N, Martins MAP (2009) Ultrasound promoted synthesis of 2-imidazolines in water: a greener approach toward monoamine oxidase inhibitors. Bioorg Med Chem Lett 19:546–549. https://doi.org/10.1016/j.bmcl.2008.03.001

    Article  PubMed  CAS  Google Scholar 

  59. Lewellyn K, Bialonska D, Chaurasiya ND, Tekwani BL, Zjawiony JK (2012) Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B. Bioorg Med Chem Lett 22:4926–4929. https://doi.org/10.1016/j.bmcl.2012.06.058

    Article  PubMed  CAS  Google Scholar 

  60. Morón JA, Campillo M, Perez V, Unzeta M, Pardo L (2000) Molecular determinants of MAO selectivity in a series of indolylmethylamine derivatives: biological activities, 3D-QSAR/CoMFA analysis, and computational simulation of ligand recognition. J Med Chem 43:1684–1691

    Article  CAS  PubMed  Google Scholar 

  61. Balansa W, Islam R, Gilbert DF, Fontaine F, Xiao X, Zhang H, Piggott AM, Lynch JW, Capon RJ (2013) Australian marine sponge alkaloids as a new class of glycine-gated chloride channel receptor modulator. Bioorg Med Chem 21:4420–4425. https://doi.org/10.1016/j.bmc.2013.04.061

    Article  PubMed  CAS  Google Scholar 

  62. Manzke T, Niebert M, Koch UR, Caley A, Vogelgesang S, Hülsmann S, Ponimaskin E, Müller U, Smart TG, Harvey RJ, Richter DW (2010) Serotonin receptor 1A–modulated phosphorylation of glycine receptor α3 controls breathing in mice. J Clin Invest 120:4118–4128. https://doi.org/10.1172/JCI43029

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Eichler SA, Kirischuk S, Jüttner R, Schafermeier PK, Legendre P, Lehmann T-N, Gloveli T, Grantyn R, Meier JC (2008) Glycinergic tonic inhibition of hippocampal neurons with depolarizing GABAergic transmission elicits histopathological signs of temporal lobe epilepsy. J Cell Mol Med 12:2848–2866. https://doi.org/10.1111/j.1582-4934.2008.00357.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Chung S-K, Vanbellinghen J-F, Mullins JGL, Robinson A, Hantke J, Hammond CL, Gilbert DF, Freilinger M, Ryan M, Kruer MC, Masri A, Gurses C, Ferrie C, Harvey K, Shiang R, Christodoulou J, Andermann F, Andermann E, Thomas RH, Harvey RJ, Lynch JW, Rees MI (2010) Pathophysiological mechanisms of dominant and recessive GLRA1 mutations in hyperekplexia. J Neurosci 30:9612–9620. https://doi.org/10.1523/JNEUROSCI.1763-10.2010

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  65. Balansa W, Islam R, Fontaine F, Piggott AM, Zhang H, Webb TI, Gilbert DF, Lynch JW, Capon RJ (2010) Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae. Bioorg Med Chem 18:2912–2919. https://doi.org/10.1016/j.bmc.2010.03.002

    Article  PubMed  CAS  Google Scholar 

  66. Ang KK, Holmes MJ, Higa T, Hamann MT, Kara UA (2000) In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. Antimicrob Agents Chemother 44:1645–1649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kochanowska AJ, Rao KV, Childress S, El-Alfy A, Matsumoto RR, Kelly M, Stewart GS, Sufka KJ, Hamann MT (2008) Secondary metabolites from three Florida sponges with antidepressant activity. J Nat Prod 71:186–189. https://doi.org/10.1021/np070371u

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Sufka KJ, Feltenstein MW, Warnick JE, Acevedo EO, Webb HE, Cartwright CM (2006) Modeling the anxiety-depression continuum hypothesis in domestic fowl chicks. Behav Pharmacol 17:681–689. https://doi.org/10.1097/FBP.0b013e3280115fac

    Article  PubMed  Google Scholar 

  69. Warnick JE, Wicks RT, Sufka KJ (2006) Modeling anxiety-like states: pharmacological characterization of the chick separation stress paradigm. Behav Pharmacol 17:581–587. https://doi.org/10.1097/01.fbp.0000236269.87547.9d

    Article  PubMed  CAS  Google Scholar 

  70. van de Waterbeemd H, Smith DA, Beaumont K, Walker DK (2001) Property-based design: optimization of drug absorption and pharmacokinetics. J Med Chem 44:1313–1333. https://doi.org/10.1021/jm000407e

    Article  CAS  Google Scholar 

  71. Bruchas MR, Schindler AG, Shankar H, Messinger DI, Miyatake M, Land BB, Lemos JC, Hagan CE, Neumaier JF, Quintana A, Palmiter RD, Chavkin C (2011) Selective p38α MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction. Neuron 71:498–511. https://doi.org/10.1016/j.neuron.2011.06.011

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Mississippi, Oxford, MS, USA

    Kevin Lewellyn

  2. Department of BioMolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, Oxford, MS, USA

    Jordan K. Zjawiony

Authors
  1. Kevin Lewellyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordan K. Zjawiony
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jordan K. Zjawiony .

Editor information

Editors and Affiliations

  1. Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Pabulo H. Rampelotto

  2. Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy

    Antonio Trincone

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lewellyn, K., Zjawiony, J.K. (2018). Aplysinopsins as Promising Marine Natural Product Drug Leads: Recent Developments. In: Rampelotto, P., Trincone, A. (eds) Grand Challenges in Marine Biotechnology. Grand Challenges in Biology and Biotechnology. Springer, Cham. https://doi.org/10.1007/978-3-319-69075-9_5

Download citation

Publish with us

Policies and ethics

Search

Navigation