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In vitro activity of aryl-thiazole derivatives against Schistosoma mansoni schistosomula and adult worms


Autoři: Adriana S. A. Pereira aff001;  Gilbert O. Silveira aff001;  Murilo S. Amaral aff001;  Sinara M. V. Almeida aff003;  Jamerson F. Oliveira aff003;  Maria C. A. Lima aff003;  Sergio Verjovski-Almeida aff001
Působiště autorů: Instituto Butantan, São Paulo, Brasil aff001;  Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil aff002;  Universidade Federal de Pernambuco, Departamento de Antibióticos, Recife, Pernambuco, Brasil aff003;  Universidade de Pernambuco, Campus Garanhuns, Garanhuns, Pernambuco, Brasil aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225425

Souhrn

Schistosomiasis is caused by a trematode of the genus Schistosoma and affects over 200 million people worldwide. The only drug recommended by the World Health Organization for treatment and control of schistosomiasis is praziquantel. Development of new drugs is therefore of great importance. Thiazoles are regarded as privileged structures with a broad spectrum of activities and are potential sources of new drug prototypes, since they can act through interactions with DNA and inhibition of DNA synthesis. In this context, we report the synthesis of a series of thiazole derivatives and their in vitro schistosomicidal activity by testing eight molecules (NJ03-08; NJ11-12) containing thiazole structures. Parameters such as motility and mortality, egg laying, pairing and parasite viability by ATP quantification, which were influenced by these compounds, were evaluated during the assays. Scanning electron microscopy (SEM) was utilized for evaluation of morphological changes in the tegument. Schistosomula and adult worms were treated in vitro with different concentrations (6.25 to 50 μM) of the thiazoles for up to 5 and 3 days, respectively. After in vitro treatment for five days with 6.25 μM NJ05 or NJ07 separately, we observed a decrease of 30% in schistosomula viability, whilst treatment with NJ05+NJ07 lead to a reduction of 75% in viability measured by ATP quantitation and propidium iodide labeling. Adult worms’ treatment with 50 μM NJ05, NJ07 or NJ05 + NJ07 showed decreased motility to 30–50% compared with controls. Compound NJ05 was more effective than NJ07, and adult worm viability after three days was reduced to 25% in parasites treated with 50 μM NJ05, compared with a viability reduction to 40% with 50 μM NJ07. SEM analysis showed severe alterations in adult worms with formation of bulges and blisters throughout the dorsal region of parasites treated with NJ05 or NJ07. Oviposition was extremely affected by treatment with the NJ series compounds; at concentrations of 25 μM and 50 μM, oviposition reached almost zero with NJ05, NJ07 or NJ05 + NJ07 already at day one. Tested genes involved in egg biosynthesis were all confirmed by qPCR as downregulated in females treated with 25 μM NJ05 for 2 days, with a significant reduction in expression of p14, Tyrosinase 2, p48 and fs800. NJ05, NJ07 or NJ05+NJ07 treatment of HEK293 (human embryonic cell line) and HES (human epithelial cell line) showed EC50 in the range of 18.42 to 145.20 μM. Overall, our results demonstrate that those molecules are suitable targets for further development into new drugs for schistosomiasis treatment, although progress is needed to lessen the cytotoxic effects on human cells. According to the present study, thiazole derivatives have schistosomicidal activities and may be part of a possible new arsenal of compounds against schistosomiasis.

Klíčová slova:

Cytotoxicity assay – Fluorescence microscopy – Oviposition – Scanning electron microscopy – Schistosoma – Schistosoma mansoni – Schistosomiasis – Thiazoles


Zdroje

1. McManus DP, Dunne DW, Sacko M, Utzinger J, Vennervald BJ, Zhou XN. Schistosomiasis. Nat Rev Dis Prim. 2018/08/11. 2018;4: 13. doi: 10.1038/s41572-018-0013-8 30093684

2. Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet. 2006/09/26. 2006;368: 1106–1118. S0140-6736(06)69440-3 [pii] doi: 10.1016/S0140-6736(06)69440-3 16997665

3. WHO. Schistosomiasis. Fact sheet accessed 20 Feb 2019. 2018;

4. Keiser J, Chollet J, Xiao SH, Mei JY, Jiao PY, Utzinger J, et al. Mefloquine—an aminoalcohol with promising antischistosomal properties in mice. PLoS Negl Trop Dis. 2009/01/07. 2009;3: e350. doi: 10.1371/journal.pntd.0000350 19125172

5. Lescano SZ, Chieffi PP, Canhassi RR, Boulos M, Amato Neto V. [Antischistosomal activity of artemether in experimental Schistosomiasis mansoni]. Rev Saude Publica. 2004/02/14. 2004;38: 71–75. doi: 10.1590/s0034-89102004000100010 [pii] 14963544

6. Kuntz AN, Davioud-Charvet E, Sayed AA, Califf LL, Dessolin J, Arner ES, et al. Thioredoxin glutathione reductase from Schistosoma mansoni: an essential parasite enzyme and a key drug target. PLoS Med. 2007/06/21. 2007;4: e206. 06-PLME-RA-0587 [pii] doi: 10.1371/journal.pmed.0040206 17579510

7. Katz N, Coelho PM. Clinical therapy of schistosomiasis mansoni: the Brazilian contribution. Acta Trop. 2008/07/12. 2008;108: 72–78. doi: 10.1016/j.actatropica.2008.05.006 [pii] 18617155

8. Siqueira LD, Fontes DAF, Aguilera CSB, Timoteo TRR, Angelos MA, Silva LCPBB, et al. Schistosomiasis: Drugs used and treatment strategies. Acta Trop. 2017;176: 179–187. doi: 10.1016/j.actatropica.2017.08.002 28803725

9. Pica-Mattoccia L, Doenhoff MJ, Valle C, Basso A, Troiani AR, Liberti P, et al. Genetic analysis of decreased praziquantel sensitivity in a laboratory strain of Schistosoma mansoni. Acta Trop. 2009/05/12. 2009;111: 82–85. doi: 10.1016/j.actatropica.2009.01.012 [pii] 19426668

10. Melman SD, Steinauer ML, Cunningham C, Kubatko LS, Mwangi IN, Wynn NB, et al. Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Negl Trop Dis. 2009; doi: 10.1371/journal.pntd.0000504 19688043

11. Doenhoff MJ, Cioli D, Utzinger J. Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis. 2008/11/04. 2008;21: 659–667. doi: 10.1097/QCO.0b013e328318978f [pii] 18978535

12. Cioli D, Pica-Mattoccia L, Basso A, Guidi A. Schistosomiasis control: praziquantel forever? Mol Biochem Parasitol. 2014/06/24. 2014;195: 23–29. doi: 10.1016/j.molbiopara.2014.06.002 24955523

13. Ross AGP, Olveda RM, Li YS. An audacious goal: the elimination of schistosomiasis in our lifetime through mass drug administration. Lancet. 2015;385: 2220–2221. doi: 10.1016/S0140-6736(14)61417-3 25467574

14. Barreiro EJ, Fraga CAM, Miranda ALP, Rodrigues CR. A química medicinal de N-acilidrazonas: novos compostos-protótipos de fármacos analgésicos, antiinflamatórios e anti-trombóticos. Quím Nov. 2002;25: 129–148. http://dx.doi.org/10.1590/S0100-40422002000100022

15. Manssour Fraga CA, Barreiro EJ. New Insights for Multifactorial Disease Therapy: The Challenge of the Symbiotic Drugs. Curr Drug ther. 2008;3: 1–13. https://doi.org/10.2174/157488508783331225

16. da Silva VBR, Campos B, de Oliveira JF, Decout JL, do Carmo Alves de Lima M. Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine. Bioorg Med Chem. 2017/05/13. 2017;25: 3259–3277. doi: 10.1016/j.bmc.2017.04.031 28495384

17. de Oliveira SA, de Oliveira Barbosa M, Filho C, Oliveira AR, de Sousa FA, de Farias Santiago E, et al. Phthalimido-thiazole as privileged scaffold: activity against immature and adult worms of Schistosoma mansoni. Parasitol Res. 2018/05/08. 2018;117: 2105–2115. doi: 10.1007/s00436-018-5897-4 29736731

18. Kubba AARM Abbas SS. Synthesis and antimicrobial evaluation of new derivatives derived from-2-amino-4-(4-nitro-/4-bromo-phenyl thiazole). Res J Pharm Biol Chem Sci. 2018;9: 235–242.

19. Mohareb RM, Abdallah AEM, Ahmed EA. Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile. Acta Pharm. 2018/01/18. 2017;67: 495–510. doi: 10.1515/acph-2017-0040 29337677

20. Ouf SA, Gomha SM, Ewies MM, Sharawy IAA. Synthesis, Characterization, and Antifungal Activity Evaluation of Some Novel Arylazothiazoles. J Heterocycl Chem. 2018;55: 258–264. doi: 10.1002/jhet.3040

21. Santiago EF, de Oliveira SA, de Oliveira Filho GB, Moreira DR, Gomes PA, da Silva AL, et al. Evaluation of the anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles. Antimicrob Agents Chemother. 2013/10/30. 2014;58: 352–363. doi: 10.1128/AAC.01900-13 24165185

22. Reddy GT, Kumar G, Reddy NCG. Water-Mediated One-pot Three-Component Synthesis of Hydrazinyl-Thiazoles Catalyzed by Copper Oxide Nanoparticles Dispersed on Titanium Dioxide Support: A Green Catalytic Process. Adv Synth Catal. 2018;360: 995–1006. doi: 10.1002/adsc.201701063

23. Mazzone G, Pignatello R, Panico A, Mazzone S, Puglisi G, Pennisi G, et al. MAOI activity of some novel series of substituted thiazol-2-yl-hydrazines. Pharmazie. 1992/12/01. 1992;47: 902–910. Available: http://www.ncbi.nlm.nih.gov/pubmed/1293612 1293612

24. Popova ZI, Tsurkan AA, Steblyuk PN. Synthesis and biological activity of some phenylazothiazoles. Farmatsevtichnii Zhurnal. 1985;6: 41–44.

25. de Oliveira Filho GB, Cardoso MVO, Espindola JWP, Oliveira ESDA, Ferreira RS, Coelho PL, et al. Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi. Eur J Med Chem. 2017/10/17. 2017;141: 346–361. S0223-5234(17)30762-6 [pii] doi: 10.1016/j.ejmech.2017.09.047 29031078

26. Lewis FA, Tucker MS. Schistosomiasis. 2014. pp. 47–75. doi: 10.1007/978-1-4939-0915-5_3 24903363

27. Duvall RH, DeWitt WB. An improved perfusion technique for recovering adult schistosomes from laboratory animals. Am J Trop Med Hyg. 1967; doi: 10.4269/ajtmh.1967.16.483 4952149

28. Basch PF. Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing. J Parasitol. 1981; doi: 10.2307/3280632

29. Horiuchi A, Satou T, Akao N, Koike K, Fujita K, Nikaido T. The effect of free and polyethylene glycol-liposome-entrapped albendazole on larval mobility and number in Toxocara canis infected mice. Vet Parasitol. 2005; doi: 10.1016/j.vetpar.2004.12.017 15817207

30. Panic G, Flores D, Ingram-Sieber K, Keiser J. Fluorescence/luminescence-based markers for the assessment of Schistosoma mansoni schistosomula drug assays. Parasites and Vectors. 2015; doi: 10.1186/s13071-015-1233-3 26644133

31. Peak E, Chalmers IW, Hoffmann KF. Development and validation of a quantitative, High-throughput, Fluorescent-based bioassay to detect schistosoma viability. PLoS Negl Trop Dis. 2010; doi: 10.1371/journal.pntd.0000759 20668553

32. Almeida GT, Lage RCG, Anderson L, Venancio TM, Nakaya HI, Miyasato PA, et al. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms. PLoS Negl Trop Dis. 2015;9: 1–23. doi: 10.1371/journal.pntd.0004086 26402251

33. Desai NN, Kennard EA, Kniss DA, Friedman CI. Novel human endometrial cell line promotes blastocyst development. Fertil Steril. 1994/04/01. 1994;61: 760–766. Available: https://www.ncbi.nlm.nih.gov/pubmed/7512055 7512055

34. Storey DM, Ogbogu VC. Observations on third-stage larvae and adults of Litomosoides carinii (Nematoda: Filarioidea) by scanning and transmission electron microscopy. Ann Trop Med Parasitol. 1991; doi: 10.1080/00034983.1991.11812537 1888208

35. Cogswell AA, Kommer VP, Williams DL. Transcriptional analysis of a unique set of genes involved in Schistosoma mansoni female reproductive biology. PLoS Negl Trop Dis. 2012/11/21. 2012;6: e1907. doi: 10.1371/journal.pntd.0001907 [pii] 23166854

36. Pereira R V., Gomes MDS, Olmo RP, Souza DM, Cabral FJ, Jannotti-Passos LK, et al. Ubiquitin-specific proteases are differentially expressed throughout the Schistosoma mansoni life cycle. Parasites and Vectors. 2015; doi: 10.1186/s13071-015-0957-4 26112833

37. Farias LP, Tararam CA, Miyasato PA, Nishiyama MY, Oliveira KC, Kawano T, et al. Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates. Parasitol Res. 2011; doi: 10.1007/s00436-010-2045-1 20852890

38. Pereira ASA, Amaral MS, Vasconcelos EJR, Pires DS, Asif H, daSilva LF, et al. Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism. PLoS Negl Trop Dis. 2018;12: e0006873. Available: doi: 10.1371/journal.pntd.0006873 30365505

39. Anderson L, Gomes MR, daSilva LF, Pereira A da SA, Mourão MM, Romier C, et al. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni. PLoS Negl Trop Dis. 2017; doi: 10.1371/journal.pntd.0005539 28406899

40. Marek M, Kannan S, Hauser AT, Moraes Mourao M, Caby S, Cura V, et al. Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke Schistosoma mansoni. PLoS Pathog. 2013/10/03. 2013;9: e1003645. doi: 10.1371/journal.ppat.1003645 [pii] 24086136

41. Wang J, Collins 3rd JJ. Identification of new markers for the Schistosoma mansoni vitelline lineage. Int J Parasitol. 2016/04/09. 2016;46: 405–410. doi: 10.1016/j.ijpara.2016.03.004 27056273

42. Utzinger J, Raso G, Brooker S, De Savigny D, Tanner M, Ornbjerg N, et al. Schistosomiasis and neglected tropical diseases: towards integrated and sustainable control and a word of caution. Parasitology. 2009/11/13. 2009;136: 1859–1874. doi: 10.1017/S0031182009991600 19906318

43. Carvalho OS, Coelho PMZ, Lenzi LH. Terapêutica experimental da esquistossomose mansoni. Schistosoma mansoni e esquistossomose: uma visão multidisciplinar. Rio de Janeiro: Editora Fiocruz; 2008. pp. 822–847.

44. de Oliveira RN, Rehder VL, Santos Oliveira AS, Junior IM, de Carvalho JE, de Ruiz AL, et al. Schistosoma mansoni: in vitro schistosomicidal activity of essential oil of Baccharis trimera (less) DC. Exp Parasitol. 2012/07/10. 2012;132: 135–143. doi: 10.1016/j.exppara.2012.06.005 22771865

45. Moraes J, Nascimento C, Lopes PO, Nakano E, Yamaguchi LF, Kato MJ, et al. Schistosoma mansoni: In vitro schistosomicidal activity of piplartine. Exp Parasitol. 2010/09/14. 2011;127: 357–364. doi: 10.1016/j.exppara.2010.08.021 20832410

46. Palusiak M, Grabowski SJ. Methoxy group as an acceptor of proton in hydrogen bonds. J Mol Struct. 2002; doi: 10.1016/S0022-2860(02)00406–4

47. Sović I, Cindrić M, Perin N, Boček I, Novaković I, Damjanović A, et al. Biological Potential of Novel Methoxy and Hydroxy Substituted Heteroaromatic Amides Designed as Promising Antioxidative Agents: Synthesis, 3D-QSAR Analysis, and Biological Activity. Chem Res Toxicol. 2019; doi: 10.1021/acs.chemrestox.9b00256 31381319

48. Kumar R, Mohanakrishnan D, Sharma A, Kaushik NK, Kalia K, Sinha AK, et al. Reinvestigation of structure-activity relationship of methoxylated chalcones as antimalarials: synthesis and evaluation of 2,4,5-trimethoxy substituted patterns as lead candidates derived from abundantly available natural beta-asarone. Eur J Med Chem. 2010/09/25. 2010;45: 5292–5301. doi: 10.1016/j.ejmech.2010.08.049 20863599

49. Bello ML, Chiaradia LD, Dias LR, Pacheco LK, Stumpf TR, Mascarello A, et al. Trimethoxy-chalcone derivatives inhibit growth of Leishmania braziliensis: synthesis, biological evaluation, molecular modeling and structure-activity relationship (SAR). Bioorg Med Chem. 2011/07/16. 2011;19: 5046–5052. doi: 10.1016/j.bmc.2011.06.023 21757358

50. Bernardes LS, Kato MJ, Albuquerque S, Carvalho I. Synthesis and trypanocidal activity of 1,4-bis-(3,4,5-trimethoxy-phenyl)-1,4-butanediol and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol. Bioorg Med Chem. 2006/08/16. 2006;14: 7075–7082. doi: 10.1016/j.bmc.2006.07.006 16908164

51. Papadopoulou M V, Bloomer WD, Rosenzweig HS, Wilkinson SR, Szular J, Kaiser M. Antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds. Eur J Med Chem. 2016/04/20. 2016;117: 179–186. doi: 10.1016/j.ejmech.2016.04.010 27092415

52. Paula FR, Serrano SHP, Tavares LC. Aspects of Bioactivity and Toxicity of Nitrocompounds. Quim Nova. 2009;32: 1013–1020. doi: 10.1590/S0100-40422009000400032

53. Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. Applications of Fluorine in Medicinal Chemistry. J Med Chem. 2015/07/23. 2015;58: 8315–8359. doi: 10.1021/acs.jmedchem.5b00258 26200936

54. Altintop MD, Atli O, Ilgin S, Demirel R, Ozdemir A, Kaplancikli ZA. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents. Eur J Med Chem. 2015/12/27. 2016;108: 406–414. doi: 10.1016/j.ejmech.2015.11.041 26706351

55. Greenberg RM. Are Ca2+ channels targets of praziquantel action? Int J Parasitol. 2004/12/28. 2005;35: 1–9. doi: 10.1016/j.ijpara.2004.09.004 15619510

56. Harder A, Goossens J, Andrews P. Influence of praziquantel and Ca2+ on the bilayer-isotropic-hexagonal transition of model membranes. Mol Biochem Parasitol. 1988/05/01. 1988;29: 55–59. Available: https://www.ncbi.nlm.nih.gov/pubmed/3386687 doi: 10.1016/0166-6851(88)90119-3 3386687

57. Lima SF, Vieira LQ, Harder A, Kusel JR. Effects of culture and praziquantel on membrane fluidity parameters of adult Schistosoma mansoni. Parasitology. 1994/07/01. 1994;109 (Pt 1): 57–64. Available: https://www.ncbi.nlm.nih.gov/pubmed/8058369

58. Craig PN. Interdependence between Physical Parametess and Selection of Substituent Groups for Correlation Studies. J Med Chem. 1971; doi: 10.1021/jm00290a004 5114063

59. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: The calcium-apoptosis link. Nat Rev Mol Cell Biol. 2003;4: 552–565. doi: 10.1038/nrm1150 12838338

60. Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 2008/10/29. 2008;27: 6407–6418. doi: 10.1038/onc.2008.308 18955969

61. You H, McManus DP, Hu W, Smout MJ, Brindley PJ, Gobert GN. Transcriptional responses of in vivo praziquantel exposure in schistosomes identifies a functional role for calcium signalling pathway member CamKII. PLoS Pathog. 2013/04/05. 2013;9: e1003254. doi: 10.1371/journal.ppat.1003254 23555262

62. Marxer M, Ingram K, Keiser J. Development of an in vitro drug screening assay using Schistosoma haematobium schistosomula. Parasit Vectors. 2012/08/11. 2012;5: 165. doi: 10.1186/1756-3305-5-165 22876861

63. Bertao HG, da Silva RAR, Padilha RJR, Albuquerque MCPA, Radis-Baptista G. Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms. Parasitol Res. 2012;110: 2465–2473. doi: 10.1007/s00436-011-2786-5 22215191

64. Taha H, Soliman ML. Antischistosomal Activity of 3-Substituted-5-(2-Aryl-2-Oxoethyl) -2, 4-Dioxo-1, 3-Thiazolidine (Ro-354). Int J Agric &BIOLOGY. 2007;09: 87–93.

65. Mohamed SH, Fawzi SM. Scanning electron microscopy on adults of Schistosoma mansoni treated in vivo with praziquantel and Ro-15(5458). Qatar Univ Sci J. 1997;17: 439–458.

66. Fawzi SM. Ultrastructural studies on the effect of antischistosomal drug Ro15-5458 on the tegument of male Schistosoma mansoni. Egypt Zool. 1999;33: 21–31.

67. Manneck T, Haggenmuller Y, Keiser J. Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni. Parasitology. 2009/10/10. 2010;137: 85–98. doi: 10.1017/S0031182009990965 19814844

68. Xiao S, Shen B, Utzinger J, Chollet J, Tanner M. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether. Mem Inst Oswaldo Cruz. 2002/09/10. 2002;97: 717–724. Available: https://www.ncbi.nlm.nih.gov/pubmed/12219141 doi: 10.1590/s0074-02762002000500023 12219141

69. Fitzpatrick JM, Hirai Y, Hirai H, Hoffmann KF. Schistosome egg production is dependent upon the activities of two developmentally regulated tyrosinases. FASEB J. 2006/12/15. 2007;21: 823–835. doi: 10.1096/fj.06-7314com 17167065

70. Bobek LA, Rekosh DM, LoVerde PT. Small gene family encoding an eggshell (chorion) protein of the human parasite Schistosoma mansoni. Mol Cell Biol. 1988/08/01. 1988;8: 3008–3016. Available: https://www.ncbi.nlm.nih.gov/pubmed/2850476 doi: 10.1128/mcb.8.8.3008 2850476

71. Chen LL, Rekosh DM, LoVerde PT. Schistosoma mansoni p48 eggshell protein gene: characterization, developmentally regulated expression and comparison to the p14 eggshell protein gene. Mol Biochem Parasitol. 1992/05/01. 1992;52: 39–52. Available: https://www.ncbi.nlm.nih.gov/pubmed/1625706 doi: 10.1016/0166-6851(92)90034-h 1625706

72. Nollen PM, Floyd RD, Kolzow RG, Deter DL. The timing of reproductive cell development and movement in Schistosoma mansoni, S. japonicum, and S. haematobium, using techniques of autoradiography and transplantation. J Parasitol. 1976/04/01. 1976;62: 227–231. Available: https://www.ncbi.nlm.nih.gov/pubmed/1263031 1263031

73. Seydoux G, Braun RE. Pathway to totipotency: lessons from germ cells. Cell. 2006/11/30. 2006;127: 891–904. doi: 10.1016/j.cell.2006.11.016 17129777

74. Wang Y, Zayas RM, Guo T, Newmark PA. nanos function is essential for development and regeneration of planarian germ cells. Proc Natl Acad Sci U S A. 2007/03/23. 2007;104: 5901–5906. doi: 10.1073/pnas.0609708104 17376870

75. Wang YY, Stary JM, Wilhelm JE, Newmark PA. A functional genomic screen in planarians identifies novel regulators of germ cell development. Genes Dev. 2010;24: 2081–2092. doi: 10.1101/gad.1951010 20844018

76. Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LC. Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res. 2006/04/26. 2006;99: 505–521. doi: 10.1007/s00436-006-0175-2 16636847


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