Parasitic diseases are a serious public health problem affecting hundreds of millions of people worldwide. African trypanosomiasis, American trypanosomiasis, leishmaniasis, malaria and toxoplasmosis are the main parasitic infections caused by protozoan parasites with over one million deaths each year. Due to old medications and drug resistance worldwide, there is an urgent need for new antiparasitic drugs. 1,3,4-Thiadiazoles have been widely studied for medical applications. The chemical, physical and pharmacokinetic properties recommend 1,3,4-thiadiazole ring as a target in drug development. Many scientific papers report the antiparasitic potential of 2-amino-1,3,4-thiadiazoles. This review presents synthetic 2-amino-1,3,4-thiadiazoles exhibiting antitrypanosomal, antimalarial and antitoxoplasmal activities. Although there are insufficient results to state the quality of 2-amino-1,3,4-thiadiazoles as a new class of antiparasitic agents, many reported derivatives can be considered as lead compounds for drug synthesis and a promise for the future treatment of parasitosis and provide a valid strategy for the development of potent antiparasitic drugs.
2. T. L. Lemke, Antiparasitic Agents, in Foye’s Principles of Medicinal Chemistry (Eds. T. L. Lemke, D. A. Williams, V. F. Roche and S. W. Zito), 7th ed., Lippincott Williams and Wilkins, Baltimore 2013, pp.1126.
3. World Health Organization, Neglected Tropical Diseases. Prevention, Control, Elimination and Eradication, Sixty-six world health assembly A66/20, Provisional agenda item 16.2, 15 March 2013; https://www.who.int/neglected_diseases/A66_20_Eng.pdf; last access date: March 27, 2019
4. P. J. Hotez, The Neglected Tropical Diseases and the Neglected Infections of Poverty: Overview of Their Common Features, Global Disease Burden and Distribution, New Control Tools, and Prospects for Disease Elimination, in Institute of Medicine (US) Forum on Microbial Threats. The Causes and Impacts of Neglected Tropical and Zoonotic Diseases: Opportunities for Integrated Intervention Strategies, National Academies Press, Washington (DC) 2011, A7; last access date March 27, 2019
5. D. Molyneux, Neglected tropical diseases, Community Eye Health J. 26 (2013) 21–24.
6. T. Furst, P. Salari, L. M. Llamas, P. Steinmann, C. Fitzpatrick and F. Tediosi, Global health policy and neglected tropical diseases: then, now and in the years to come, PLoS Negl. Trop. Dis. 11 (2017) e0005759; https://doi.org/10.1371/journal.pntd.0005759
7. F. Pourrajab, S. K. Forouzannia and S. A. Tabatabaee, Novel immunomodulatory function of 1,3,4-thiadiazole derivatives with leishmanicidal activity, J. Antimicrob. Chemother.67 (2012) 1968–1978; https://doi.org/10.1093/jac/dks144
8. J. A. Joule, Natural Products Containing Nitrogen Heterocycles – Some Highlights 1990-2015, in Advances in Heterocyclic Chemistry: Heterocyclic Chemistry in the 21st Century – A Tribute to Alan Katritzky (Eds. E. F. V. Scriven and C. A. Ramsden), 1st ed., Academic Press, Cambridge (MA) 2016, Vol. 119, pp. 81–106.
9. S. B. A. M. W. Van den Broek, S. A. Meeuwissen, F. L. van Delft and F. P. J. T. Rutjes, Natural Products Containing Medium-Sized Nitrogen Heterocycles Synthesized by Ring-Closing Alkene Metathesis, in Metathesis in Natural Product Synthesis: Strategies, Substrates and Catalysts (Eds. J. Cossy, S. Arseniyadis and C. Meyer), Wiley-VCH, Weinheim 2010, pp. 45–85.
10. F. Diaba, J. A.Montiel, G. Serban and J. Bonjoch, Synthesis of normorphans through an efficient intramolecular carbamoylation of ketones, Org. Lett.17 (2015) 3860–3863; https://doi.org/10.1021/acs.orglett.5b01832
11. G. Serban, H. Abe and Y. Takeuchi, Synthetic studies of substituted pyridine aldehydes as intermediates for the synthesis of toddaquinoline, its derivatives and other natural products, Heterocycles83 (2011) 1989–2000; https://doi.org/10.3987/COM-11-12239
12. G. Serban, H. Abe, Y. Takeuchi and T. Harayama, A new approach to the benzopyridoxepine core by metal mediated intramolecular biaryl ether formation, Heterocycles75 (2008) 2949–2958; https://doi.org/10.3987/COM-08-11443
13. G. Serban, Y. Shigeta, H. Nishioka, H. Abe, Y. Takeuchi and T. Harayama, Studies toward the synthesis of toddaquinoline by intramolecular cyclization, Heterocycles71 (2007) 1623–1630; https://doi.org/10.3987/COM-07-11062
14. D. Sole, F. Diaba and J. Bonjoch, Nitrogen heterocycles by palladium-catalyzed cyclization of amino-tethered vinyl halides and ketone enolates, J. Org. Chem.68 (2003) 5746–5749; https://doi.org/10.1021/jo034299q
16. P. K. Shukla, A. Verma and P. Mishra, Significance of Nitrogen Heterocyclic Nuclei in the Search of Pharmacological Active Compounds, in New Perspective in Agricultural and Human Health (Eds. R. P. Shukla, R. S. Mishra, A. D. Tripathi, A. K. Yadav, M. Tiwari and R. R. Mishra), Bharti Publication, New Delhi 2017, pp. 100–126.
17. P. Martins, J. Jesus, S. Santos, L. R. Raposo, C. Roma-Rodrigues, P. V. Baptista and A. R. Fernandes, Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box, Molecules20 (2015) 16852–16891; https://doi.org/10.3390/molecules200916852
19. A. V. Fuentes, M. D. Pineda and K. C. N. Venkata, Comprehension of top 200 prescribed drugs in the US as a resource for pharmacy teaching, training and practice, Pharmacy6 (2018) 43–52; https://doi.org/10.3390/pharmacy6020043
21. J. Keiser, K. Ingram and J. Utzinger, Antiparasitic drugs for paediatrics: systemic review, formulations, pharmacokinetcs, safety, efficacy and implications for control, Parasitology138 (2011) 1620–1632; https://doi.org/10.1017/S0031182011000023
24. M. Yoosefian, Z. J. Chermahini, H. Raissi, A. Mola and M. Sadeghi, A theoretical study on the structure of 2-amino-1,3,4-thiadiazole and its 5-substituted derivatives in the gas phase, water, THF and DMSO solutions, J. Mol. Liq.203 (2015) 137–142; https://doi.org/10.1016/j.molliq.2015.01.002
27. G. Serban, O. Stanasel, E. Serban and S. Bota, 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents, Drug Des. Devel. Ther.12 (2018) 1545–1566; https://doi.org/10.2147/DDDT.S155958
28. M. G. Yang, T. G. M. Dhar, Z. Xiao, H. Y. Xiao, J. J. W. Duan, B. Jiang, M. A. Galella, M. Cunningham, J. Wang, S. Habte, D. Shuster, K. W. McIntyre, J. Carman, D. A. Holloway, J. E. Somerville, S. G. Nadler, L. Salter-Cid, J. C. Barrish and D. S. Weinstein, Improving the pharmacokinetic and CYP inhibition profiles of azaxanthene-based glucocorticoid receptor modulators – Identification of (S)-5-(2-(9-fluoro-2-(4-(2-hydroxypropan-2-yl)phenyl)-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropan amido)-N-(tetrahydro-2H-pyran-4-yl)-1,3,4-thiadiazole-2-carboxamide (BMS-341), J. Med. Chem.58 (2015) 4278–4290; https://doi.org/10.1021/acs.jmedchem.5b00257
29. Y. J. Wu, Five-membered ring systems: with N and S atom, in Progress in Heterocyclic Chemistry (Eds. G. W. Gribble and J. A. Joule), Elsevier, Amsterdam 2017, Vol. 29, pp. 315–335.
30. R. Sink, I. Sosic, M. Zivec, R. Fernandez-Menendez, S. Turk, S. Pajk, D. Alvarez-Gomez, E. M. Lopez-Roman, C. Gonzales-Cortez, J. Rullas-Triconado, I. Angulo-Barturen, D. Barros, L. Ballell-Pages, R. J. Young, L. Encinas and S. Gobec, Design, synthesis and evaluation of new thiadiazole based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis, J. Med. Chem.58 (2015) 613–624;https://doi.org/10.1021/jm501029r
31. F. Hipler, M. Winter and R. A. Fischer, N-H…S hydrogen bonding in 2-mercapto-5-methyl-1,3,4-thiadiazole. Synthesis and crystal structures of mercapto functionalized 1,3,4-thiadiazoles, J. Mol. Struct.658 (2003) 179–191; https://doi.org/10.1016/S0022-2860(03)00386-7
32. Y. Hu, C. Y. Li, X. M. Wang, Y. H. Yang and H. L. Zhu, 1,3,4-Thiadiazole: synthesis, reactions and applications in medicinal, agricultural, and materials chemistry, Chem. Rev.114 (2014) 5572–5610; https://doi.org/10.1021/cr400131u
33. A. T. Balaban, D. C. Oniciu and A. R. Katritzky, Aromaticity as a cornerstone of heterocyclic chemistry, Chem. Rev.104 (2004) 2777–2812;https://doi.org/10.1021/cr0306790
34. G. Kornis, Five-membered Rings with More than Two Heteroatoms and Fused Carbocyclic Derivatives, in Comprehensive Heterocyclic Chemistry II (Eds. A. R. Katritzky, C. W. Rees and E. F. V. Scriven), Elsevier, Oxford 1996, Volume 4, pp. 379–408.
35. A. Senff-Ribeiro, A. Echevarria, E. F. Silva, C. R. C. Franco, S. S. Veiga and M. B. M. Oliveira, Cytotoxic effect of a new 1,3,4-thiadiazolium mesoionic compound (MI-D) on cell lines of human mellanoma, Br. J. Cancer91 (2004) 297–304; https://doi.org/10.1038/sj.bjc.6601946
36. M. M. Ciotti, S. R. Humphreys, J. M. Venditti, N. O. Kaplan and A. Goldin, The antileukemic action of two thiadiazole derivatives, Cancer Res.20 (1960) 1195–1201.
37. M. Juszczak, J. Matysiak, W. Brzana, A. Niewiadomy and W. Rzeski, Evaluation of antiproliferative activity of 2-(monohalogenophenylamino)-5-(2, 4-dihydroxyphenyl)-1,3,4-thiadiazoles, Arzneim. Forsch. Drug Res.58 (2008) 353–357; https://doi.org/10.1055/s-0031-1296519
38. J. Matysiak, Evaluation of antiproliferative effect in vitro of some 2-amino-5-(2, 4-dihydroxyphenyl)-1,3,4-thiadiazole derivatives, Chem. Pharm. Bull.54 (2006) 988–991; https://doi.org/10.1248/cpb.54.988
39. J. Matysiak and A. Opolski, Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles, Bioorg. Med. Chem.14 (2006) 4483–4489; https://doi.org/10.1016/j.bmc.2006.02.027
40. W. Rzeski, J. Matysiak and M. Kandefer-Szerszen, Anticancer, neuroprotective activities and computational studies of 2-amino-1,3,4-thiadiazole based compound, Bioorg. Med.Chem.15 (2007) 3201–3207; https://doi.org/10.1016/j.bmc.2007.02.041
41. R. Asbury, J. A. Blessing and D. Moore, A phase II trial of aminothiadiazole in patients with mixed mesodermal tumors of the uterine corpus: a gynecologic oncology group study, Am. J. Clin. Oncol.19 (1996) 400–402.
42. P. L. Elson, L. K. Kvols, S. E. Vogl, D. J. Glover, R. G. Hahn and D. L. Trump, Phase II trials of 5-day vinblastine infusion (NSC 49842), L-alanosine (NSC153353), acivicin (NSC 163501), and aminothiadiazole (NSC 4728) in patients with recurrent or metastatic renal cell carcinoma, Invest. New Drugs6 (1988) 97–103.
43. P. F. Engstrom, L. M. Ryan, G. Falkson and D. G. Haller, Phase II study of aminothiadiazole in advanced squamous cell carcinoma of the esophagus, Am. J. Clin. Oncol.14 (1991) 33–35.
44. G. Y. Locker, L. Kilton, J. D. Khandekar, T. E. Lad, R. H. Knop, K. Albain, R. Blough, S. French and A. B. Benson, High-dose aminothiadiazole in advanced colorectal cancer. An Illinois Cancer Center phase II trial, Invest. New Drugs12 (1994) 299–301.
46. H. F. Oettgen, J. A. Reppert, V. Coley and J. H. Burchenal, Effects of nicotinamide and related compounds on the antileukemic activity of 2-amino-1,3,4-thiadiazole, Cancer Res. 20 (1960) 1597–1601.
47. D. M. Shapiro, M. E. Shils, R. A. Fugmann andI. M. Friedland, Quantitative biochemical differences between tumor and host as a basis for cancer chemotherapy IV. Niacin and 2-ethylamino-1,3,4-thiadiazole, Cancer Res. 17 (1957) 29–33.
58. P. Linciano, A. Dawson, I. Poohner, D. M. Costa, M. S. Sa, A. Cordeiro-da-Silva, R. Luciani, S. Gul, G. Witt, B. Ellinger, M. Kuzikov, P. Gribbon, J. Reinshagen, M. Wolf, B. Behrens, V. Hannaert, P. A. M. Michels, E. Nerini, C. Pozzi, F. di Pisa, G. Landi, N. Santarem, S. Ferrari, P. Saxena, S. Lazzari, G. Cannazza, L. H. Freitas-Junior, C. B. Moraes, B. S. Pascoalino, L. M. Alcantara, C. P. Bertolacini, V. Fontana, U. Wittig, W. Muller, R. C. Wade, W. N. Hunter, S. Mangani, L. Costantino and M. P. Costi, Exploiting the 2-amino-1,3,4-thiadiazole scaffold to inhibit Trypanosoma brucei pteridine reductase in support of early-stage drug discovery, ACS Omega2 (2017) 5666−5683; https://doi.org/10.1021/acsomega.7b00473
61. S. Patterson and S. Wyllie, Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects, Trend Parasitol.30 (2014) 289–298; https://doi.org/10.1016/j.pt.2014.04.003
64. A. K. Jain, S. Sharma, A. Vaidya, V. Ravichandran and R. K. Agrawal, 1,3,4-Thiadiazole and its derivatives: a review on recent progress in biological activities, Chem. Biol. Drug Des.81 (2013) 557–576; https://doi.org/10.1111/cbdd.12125
65. S. Tomlinson, F. Vandekerckhove, U. Frevert and V. Nussenzweig, The induction of Trypanosoma cruzi trypomastigote transformation by low pH, Parasitology110 (1995) 547–554; https://doi.org/10.1017/S0031182000065264
66. A. S. Nagle, S. Khare, A. B. Kumar, F. Supek, A. Buchynskyy, C. J. N. Mathison, N. K. Chennamaneni, N. Pendem, F. S. Buckner, M. H. Gelb and V. Molteni, Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis, Chem. Rev.114 (2014) 11305–11347; https://doi.org/10.1021/cr500365f
73. S. Pund and A. Joshi, Nanoarchitectures for Neglected Tropical Diseases: Challenges and State of the Art, in Nano- and Microscale Drug Delivery Systems: Design and Fabrication (Ed. A. M. Grumezescu), 1st ed., Elsevier, Amsterdam 2017, pp. 449.
74. J. D. Maya, S. Bollo, L. J. Nunez-Vergara, J. A. Squella, Y. Repetto, A. Morello, J. Perie and G. Chauviere, Trypanosoma cruzi: effect and mode of action of nitroimidazole and nitrofuran derivatives, Biochem. Pharmacol.65 (2003) 999–1006; https://doi.org/10.1016/S0006-2952(02)01663-5
75. A. Silva de Carvalho, K. Salomao, S. Lisboa de Castro, T. R. Conde, H. P. da Silva Zamith, E. R. Caffarena, B. S. Hall, S. R. Wilkinson and N. Boechat, Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme, Mem. Inst. Oswaldo Cruz109 (2014) 315–323; https://doi.org/10.1590/0074-0276140497
76. B. Bouteille, A. Marie-Daragon, G. Chauviere, C. de Albuquerque, B. Enanga, M. L. Darde, J. M. Vallat, J. Perie and M. Dumas, Effect of megazol on Trypanosoma brucei brucei acute and subacute infections in Swiss mice, Acta Tropica60 (1995) 73–80; https://doi.org/10.1016/0001-706X(95)00109-R
77. G. Chauviere, B. Bouteille, B. Enanga, C. de Albuquerque, S. L. Croft, M. Dumas and J. Perie, Synthesis and biological activity of nitro heterocycles analogous to megazol, a trypanocidal lead, J. Med. Chem.46 (2003) 427–440; https://doi.org/10.1021/jm021030a
79. B. Enanga, M. R. Ariyanayagam, M. L. Stewart and M. P. Barrett, Activity of megazol, a trypanocidal nitroimidazole, is associated with DNA damage, Antimicrob. Agents Chemother.47 (2003) 3368–3370; https://doi.org/10.1128/AAC.47.10.3368-3370.2003
80. H. B. Leites, F. S. Damasceno, A. M. Silber, R. Z. Mendonca and C. N. Albuquerque, Synthesis and evaluation of trypanosomicidal activity of new derivatives of megazol, Pharm. Biol. Eval.5 (2018) 40–51.
83. H. B. Ong, N. Sienkiewicz, S. Wyllie and A. H. Fairlamb, Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma bruceiand Leishmania major, J. Biol. Chem.286 (2011) 10429–10438; https://doi.org/10.1074/jbc.M110.209593
84. S. Ferrari, F. Morandi, D. Motiejunas, E. Nerini, S. Henrich, R. Luciani, A. Venturelli, S. Lazzari, S. Calo, S. Gupta, V. Hannaert, P. A. M. Michels, R. C. Wade and M. P. Costi, Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase, J. Med. Chem.54 (2011) 211–221; https://doi.org/10.1021/jm1010572
85. A. Dawson, F. Gibellini, N. Sienkiewicz, L. B. Tulloch, P. K. Fyfe, K. McLuskey, A. H. Fairlamb and W. N. Hunter, Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate, Mol. Microbiol.61 (2006) 1457–1468; https://doi.org/10.1111/j.1365-2958.2006.05332.x
86. D. Spinks, H. B. Ong, C. P. Mpamhanga, E. J. Shanks, D. A. Robinson, I. T. Collie, K. D. Read, J. A. Frearson, P. G. Wyatt, R. Brenk, A. H. Fairlamb and I. H. Gilbert, Design, synthesis and biological evaluation of novel inhibitors of Trypanosoma brucei pteridine reductase 1, Chem. Med. Chem.6 (2011) 302–308; https://doi.org/10.1002/cmdc.201000450
87. B. Nare, J. Luba, L. W. Hardy and S. Beverley, New approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity, Parasitology114 (1997) S101–S110.
88. A. Cavazzuti, G. Paglietti, W. N. Hunter, F. Gamarro, S. Piras, M. Loriga, S. Allecca, P. Corona, K. McLuskey, L. Tulloch, F. Gibellini, S. Ferrari and M. P. Costi, Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development, Proc. Natl. Acad. Sci. USA105 (2008) 1448–1453; https://doi.org/10.1073/pnas.0704384105
89. R. F. Rodrigues, D. Castro-Pinto, A. Echevarria, C. M. dos Reis, C. N. Del Cistia, C. M. R. Sant’Anna, F. Teixeira, H. Castro, M. Canto-Cavalheiro, L. L. Leon and A. Tomas, Investigation of trypanothione reductase inhibitory activity by 1,3,4-thiadiazolium-2-aminide derivatives and molecular docking studies, Bioorg. Med. Chem.20 (2012) 1760–1766; https://doi.org/10.1016/j.bmc.2012.01.009
90. G. Colotti, P. Baiocco, A. Fiorillo, A. Boffi, E. Poser, F. Di Chiaro and A. Ilari, Structural insights into the enzymes of the trypanothione pathway: Targets for antileishmaniasis drugs, Future Med. Chem. 5 (2013) 1861–1875; https://doi.org/10.4155/fmc.13.146
91. M. O. F. Khan, Trypanothione reductase: A viable chemotherapeutic target for antitrypanosomal and antileishmanial drug design, Drug Target Insights2 (2007) 129–146; https://doi.org/10.1177/117739280700200007
92. D. Benítez, A. Medeiros, L. Fiestas, E. A. Panozzo-Zenere, F. Maiwald, K. C. Prousis, M. Roussaki, T. Calogeropoulou, A. Detsi, T. Jaeger, J. Šarlauskas, L. P. Mašič, C. Kunick, G. R. Labadie, L. Flohé and M. A. Comini, Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids, PLoS Negl. Trop. Dis.10 (2016) e0004617 (25 pages); https://doi.org/10.1371/journal.pntd.0004617
93. A. Ilari, A. Fiorillo, I. Genovese and G. Colotti, An update on structural insights into the enzymes of the polyamine-trypanothione pathway: targets for new drugs against leishmaniasis, Future Med. Chem.9 (2017) 61–77; https://doi.org/10.4155/fmc-2016-0180
94. V. Olin-Sandoval, Z. Gonzalez-Chavez, M. Berzunza-Cruz, I. Martinez, R. Jasso-Chavez, I. Becker, B. Espinoza, R. Moreno-Sanchez and E. Saavedra, Drug target validation of the trypanothione pathway enzymes through metabolic modeling, FEBS J.279 (2012) 1811–1833; https://doi.org/10.1111/j.1742-4658.2012.08557.x
95. R. F. Rodrigues, E. F. da Silva, A. Echevarria, R. Fajardo-Bonin, V. F. Amaral, L. L. Leon and M. Canto-Cavalheiro, A comparative study of mesoionic compounds in Leishmania sp. and toxicity evaluation, Eur. J. Med. Chem. 42 (2007) 1039–1043; https://doi.org/10.1016/j.ejmech.2006.12.026
96. R. F. Rodrigues, K. S. Charret, E. F. da Silva, A. Echevarria, V. F. Amaral, L. L. Leon and M. Canto-Cavalheiro, Antileishmanial activity of 1,3,4-thiadiazolium-2-aminide in mice infected with Leishmania amazonensis, Antimicrob. Agents Chemother. 53 (2009) 839–842; https://doi.org/10.1128/AAC.00062-08
97. D. Spinks, L. S. Torrie, S. Thompson, J. R. Harrison, J. A. Frearson, K. D. Read, A. H. Fairlamb, P. G. Wyatt and I. H. Gilbert, Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors, Chem. Med. Chem.7 (2012) 95–106; https://doi.org/10.1002/cmdc.201100420
98. A. F. Sousa, A. G. Gomes-Alves, D. Benitez, M. A. Comini, L. Flohe, T. Jaeger, J. Passos, F. Stuhlmann, A. M. Tomas and H. Castro, Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantu, Free Radic. Biol. Med.73 (2014) 229–238; https://doi.org/10.1016/j.freeradbiomed.2014.05.007
99. P. K. Fyfe, S. L. Oza, A. H. Fairlamb and W. N. Hunter, Leishmania trypanothione synthetaseamidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities, J. Biol. Chem.283 (2008) 17672–17680; https://doi.org/10.1074/jbc.M801850200
100. W. da Silva Ferreira, L. Freire-de-Lima, V. Barbosa Saraiva, F. Alisson-Silva, L. Mendonca-Previato, J. O. Previato, A. Echevarria and M. E. Freire de Lima, Novel 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: chemical and biological studies, Bioorg. Med. Chem.16 (2008) 2984–2991; https://doi.org/10.1016/j.bmc.2007.12.049
101. A. Tahghighi and F. Babalouei, Thiadiazoles: the appropriate pharmacological scaffolds with leishmanicidal and antimalarial activities: a review, Iran. J. Basic Med. Sci.20 (2017) 613–622; https://doi.org/10.22038/IJBMS.2017.8828
107. L. Foquet, C. Hermsen, G. J. van Gemert, E. Van Braeckel, K. Weening, R. Sauerwein, P. Meuleman and G. Leroux-Roels, Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection, J. Clin. Invest.124 (2014) 140–144; https://doi.org/10.1172/JCI70349
111. P. B. Bloland and H. A. Williams, Malaria Control During Mass Population Movements and Natural Disasters, National Academies Press, Washington (DC) 2002, pp. 145–150.
112. V. M. Avery, S. Bashyam, J. N. Burrows, S. Duffy, G. Papadatos, S. Puthukkuti, Y. Sambandan, S. Singh, T. Spangenberg, D. Waterson and P. Willis, Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum, Malar. J.13 (2014) Article ID 190 (12 pages); https://doi.org/10.1186/1475-2875-13-190
113. E. G. Severance, J. Xiao, L. Jones-Brando, S. Sabunciyan, Y. Li, M. Pletnikov, E. Prandovszky and R. Yolken, Toxoplasma gondii – a gastrointestinal pathogen associated with human brain diseases, Int. Rev. Neurobiol.131 (2016) 143–163; https://doi.org/10.1016/bs.irn.2016.08.008
114. P. R. Torgerson and P. Mastroiacovo, The global burden of congenital toxoplasmosis: a systematic review, Bull. World Health Organ.91 (2013) 501–508.
117. K. Dzitko, A. Paneth, T. Plech, J. Pawelczyk, P. Staczek, J. Stefanska and P. Paneth, 1,4-Disubstituted thiosemicarbazide derivatives are potent inhibitors of Toxoplasma gondii proliferation, Molecules19 (2014) 9926–9943; https://doi.org/10.3390/molecules19079926
119. R. P. Tenorio, C. S. Carvalho, C. S. Pessanha, J. G. de Lima, A. R. de Faria, A. J. Alves, E. J. T. de Melo and A. J. S. Goes, Synthesis of thiosemicarbazone and 4-thiazolidinone derivatives and their in vitro anti-Toxoplasma gondii activity, Bioorg. Med. Chem. Lett.15 (2005) 2575–2578; https://doi.org/10.1016/j.bmcl.2005.03.048
120. T. M. de Aquino, A. P. Liesen, R. E. A. da Silva, V. T. Lima, C. S. Carvalho, A. R. de Faria, J. M. de Araujo, J. G. de Lima, A. J. Alves, E. J. T. de Melo and A. J. S. Goes, Synthesis, anti-Toxoplasma gondii and antimicrobial activities of benzaldehyde 4-phenyl-3-thiosemicarbazones and 2-[(phenylmethylene)hydrazono]-4-oxo-3-phenyl-5-thiazolidineacetic acids, Bioorg. Med. Chem.16 (2008) 446–456; https://doi.org/10.1016/j.bmc.2007.09.025
121. A. P. Liesen, T. M. de Aquino, C. S. Carvalho, V. T. Lima, J. M. de Araujo, J. G. de Lima, A. R. de Faria, E. J. T. de Melo, A. J. Alves, E. W. Alves, A. Q. Alves and A. J. S. Goes, Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles, Eur. J. Med. Chem.45 (2010) 3685–3691; https://doi.org/10.1016/j.ejmech.2010.05.017