Synthesis and preliminary ex vivo evaluation of the spasmolytic activity of 1,3-thiazolium- and 1,3,4-thiadiazolium-5-methylthio- and 5-thioacetate derivatives

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Seven new compounds have been synthetized in satisfactory yields (51-78 %) through the treatment of mesoionic 1,3-thiazolium-5-thiolate (4a-d) and 1,3,4-thiadiazolium- 5-thiolate (10a,b) with chloroacetic acid or methyl iodide: 1,3,4-thiadiazolium-5-methylthio- (11) and 5-thioacetate (12). The structure of the title compounds was elucidated by elemental analysis, IR, 1H and 13C NMR spectroscopy. The newly synthesized compounds 5a, 6a, 11 and 12 were evaluated for their ex vivo spasmolytic potential on four isolated smooth muscles (rat aorta and uterus, guinea pig ileum and trachea) and compared with scopolamine. Some of the compounds exhibited potent spasmolytic activity equal to or stronger than scopolamine

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  • 1. L. B. Kier and E. B. Roche Medicinal chemistry of the mesoionic compounds J. Pharm. Sci. 56 (1966) 149-168; DOI: 10.1002/jps.2600560202.

  • 2. M. B. Oliveira J. Miller A. B. Pereira S. E. Galembeck G. L. C. Moura and A. M. Simas Mesoionic 2-N-cycloalkylamino-5-alkyl-13-dithiolium-4-thiolates Phosphorus Sulfur Silicon Relat. Elem. 108 (1996) 75-84; DOI: 10.1080/10426509608029640.

  • 3. C. A. C. Bosco G. S. Maciel N. Rakov C. B. Araújo L. H. Acioli A. M. Simas P. F. Athayde- -Filho and J. Miller Probing the nuclear susceptibility of mesoionic compounds using two-beam coupling with chirp-controlled pulses Chem. Phys. Lett. 449 (2007) 101-106; DOI: 10.1016/ j.cplett.2007.10.037.

  • 4. R. S. T. R. Nascimento C. R. S. Morais H. L. Lira S. A. Morais P. F. Athayde-Filho L. F. L. Lucena A. G. Souza and G. B. Campos Synthesis and characterization of nanocomplexes of Eu(III) and Er(III) coordinate with 2(4-clorophenyl)-3-phenyl-134-thiadiazoleo-5-tiolate mesoionic J. Alloys Comp. 495 (2010) 603-605; DOI: 10.1016/j.jallcom.2009.12.003.

  • 5. S. A.Morais C. R. S. Morais P. F. Athayde-Filho B. F. Lira and R. S. T. R. Nascimento Akinetic study of the thermal decomposition of mesoionic compounds within scope of its application in nonlinear optical devices J. Therm. Anal. Calorim. 97 (2009) 437-441; DOI: 10.1007/s10973-009-0082-8.

  • 6. B. F. Lira S. A. Morais G. B. Rocha J. Miller G. L. C. Moura A. M. Simas C. Peppe and P. F. Athayde-Filho 13-Thiazolium-5-thiolates mesoionic compounds: Semiempirical evaluation of their first static hyperpolarizabilities and synthesis of new examples J. Braz. Chem. Soc. 21 (2010) 934-940; DOI: 101590/S0103-505320100000500024.

  • 7. A. S.-Ribeiro A. Echevarria E. F. Silva C. R. C. Franco S. S. Veiga and M. B. M. Oliveira Cytotoxic effect of a new 134-thiadiazolium mesoionic compound (MI-D) on cell lines of human melanoma Br. J. Cancer 91 (2004) 297-304. DOI: 10.1038/sj.bjc.6601946.

  • 8. R. F. Rodrigues E. F. Silva A. Echevarria R. Fajardo-Bonin V. F. Amaral L. L. Leon and M. M. Canto-Cavalheiro A comparative study of mesoionic compounds in Leishmania sp. and toxicity evaluation Eur. J. Med. Chem. 42 (2007) 1039-1043; DOI: 10.1016/j.ejmech.2006.12.026.

  • 9. R. F. Rodrigues D. Castro-Pinto A. Echevarria C.M. Reis C. N. Del Cistia C. M. R. Sant’Anna F. Teixeira H. Castro M. Canto-Cavalheiro L. L. Leon and A. Tomás Investigation of tripanothione redutase inhibitory activity by 134-thiadiazolium-2-aminide derivatives and molecular docking studies Bioorg. Med. Chem. 20 (2012) 1760-1766; DOI: 10.1016/j.bmc.2012.01.009.

  • 10. K. L. M. Cavalcante N. A. Correia K. L. G. Dias D. F. Silva J. C. Silva-Filho I. G. A. Araújo B. F. Lira P. F. Athayde-Filho and I. A. Medeiros Endothelium-derived nitric oxide contributes to the vasorelaxant response induced by mesoionic 2-(4-chlorophenyl)-3-methyl-4-(4-methoxyphenyl)-13-thiazolium-5-thyolate (CMMTT) in rats J. Pharmacol. Sci. 110 (2009) 29-35; DOI: 10.1254/jphs.FP0071581.

  • 11. K. Rehse T. Ciborski and B. Müller Platelet aggregation inhibiting and anticoagulant effects of oligoamines. XXVII. Inhibition of leucocyte adherence to endothelium by oligoamine RE 1492C and the NO-donor RE 2047 Arch. Pharm. (Weinheim) 328 (1995) 125-126; DOI: 10.1002/ardp. 19953280206.

  • 12. L. B. Kier and E. B. Roche Medicinal chemistry of the mesoionic compounds J. Pharm. Sci. 56 (1967) 149-168; DOI: 10.1002/jps.2600560202.

  • 13. C. S. Oliveira V. S. Falcão-Silva J. P. Siqueira-Júnior D. P. Harding B. F. Lira J. G. F. Lorenzo J. M. Barbosa-Filho and P. F. Athayde-Filho Drug resistance modulation in Staphylococcus aureus a new biological activity for mesoionic hydrochloride compounds Molecules 16 (2011) 2023-2031; DOI: 10.3390/molecules16032023.

  • 14. B. F. Lira J. Miller A. M. Simas P. F. Athayde-Filho A. F. Dias R. O. Silva and V. C. Oliveira Synthesis and complete assignments of 1H and 13C-NMR spectra of mesoionic 2-(p-trifluoromethylphenyl)-3-methyl-4-(p-tolyl)-13-thiazolium-5-thiolate and 2-(p-chlorophenyl)-3-methyl-4-(p-isopropylphenyl)-13-thiazolium-5-thiolate Arkivoc vi (2004) 12-21.

  • 15. P. F. Athayde-Filho J. Miller A. M. Simas K. X. F. R. Sena and A. A. Chiappeta Synthesis characterization and evaluation of the activity of ten mesoionic compounds against microorganisms Lat. Am. J. Pharm. 18 (1999) 17-22.

  • 16. J. T. Lima J. R. G. S. Almeida K. S. L.Mota A. S. S. C. Lúcio C. A. Câmara J.M. B. Filho and B. A. Silva Selective spasmolytic effect of a new furanoflavoquinone derivative from diplotropin on guinea-pig trachea J. Chem. Pharm. Res. 3 (2011) 249-258.

  • 17. E. E. Daniel C. Y. Kwan and L. Janssen Pharmacological techniques for the in vitro study of intestinal smooth muscles J. Pharmacol. Toxicol. Meth. 45 (2001) 141-158.

  • 18. B. M. Altura and B. T. Altura Differential effects of substrate depletion on drug-induced contractions of rabbit aorta Am. J. Physiol. 219 (1970) 1698-1705.

  • 19. E. Tschirhart N. Frossard C. Bertrand and Y. Landry Arachidonic acid metabolites and airway epithelium-dependent relaxant factor J. Pharmacol. Exp. Ther. 243 (1987) 310-316.

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