S Tomasi

Publications (9)11.58 Total impact

• Article: Depletion of Polyamines Potentiates the Antitumour Effect of Tetracyclic Amidines Bearing a Putrescine Moiety

  S. TOMASI, V. L. EIFLER-LIMA, M. LE ROCH, J. C. CORBEL, J. RENAULT, P. URIAC, T. MENS, V. CATROS-QUEMENER, J. P. MOULINOUX
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  ABSTRACT: D, L-2-(Difluoromethyl) ornithine (DFMO), a potent inactivator of putrescine biosynthesis that depletes spermidine levels in cells, is known to enhance cytotoxicity of DNA-binding drugs. A significant in-vitro cytotoxicity and DNA-binding affinity found for amidines containing both heterocyclic and polyamine moieties prompted us to evaluate their in-vivo activity on Lewis lung carcinoma (3LL).When administered alone to tumour bearing mice, neither DFMO nor the tetracyclic amidines were effective. However, their combined administration with DFMO inhibited tumour growth significantly.
  Pharmacy and Pharmacology Communications. 03/2011; 3(5‐6):241 - 247.
• Article: N‐alkylation of N1‐mesitylenesulphonylputrescine with N‐(4‐bromobutyl)phthalimide: A Parallel Approach Using Multipin Solid‐phase Synthesis

  S. TOMASI, M. LE ROCH, J. RENAULT, J. C. CORBEL, P. URIAC
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  ABSTRACT: Many problems are encountered in the synthesis of polyamines, natural compounds of biological interest. We describe here the rapid optimization of experimental conditions for the synthesis of orthogonally substituted triamines starting from simple building blocks-diamines and bromoalkylphthalimides. For this purpose we have adapted Bergeron's liquid-phase method (N-alkylation of sulphonamides) to solid-phase organic synthesis. The solid support was Multipin crowns enabling rapid optimization of the key-step-deprotonation of the sulphonamide. The combination of different building-blocks could lead to wide diversity.
  Pharmacy and Pharmacology Communications. 02/2010; 6(4):155 - 159.
• Article: Solid‐phase Organic Synthesis of Unnatural Polyamine Analogues Bearing a Dansyl or Acridine Moiety

  S. CARRINGTON, J. RENAULT, S. TOMASI, S. SINBANDHIT, I. S. BLAGBROUGH, P. URIAC
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  ABSTRACT: The synthesis of unnatural polyamines and polyamine conjugates from a protected triamine anchored to Wang resin is described. The use of solid-phase organic synthesis for such hydrophilic compounds is of interest because it removes the need for often awkward chromatographic purification of intermediates and is easily applied to the synthesis of compound libraries. Chain elongation was achieved by reductive amination and the resulting resin bound tetraamine was functionalized with dansyl and acridine moieties. The conjugates were cleaved from the resin and these studies should lead to the rapid synthesis of libraries for biological evaluation.
  Pharmacy and Pharmacology Communications. 02/2010; 5(3):151 - 157.
• Article: Cytotoxic activity of methanol extracts from Basidiomycete mushrooms on murine cancer cell lines.

  S Tomasi, F Lohézic-Le Dévéhat, P Sauleau, C Bézivin, J Boustie
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  ABSTRACT: Crude methanol extracts of 58 mushroom species were screened for their cytotoxic activities against two murine cancer cell lines, L1210 and 3LL, using the tetrazolium assay. A majority of extracts (74%) exhibited IC50 > 100 microg/ml against both cell lines. A most marked activity against one of the cell lines was noted for nine species (14% of the tested species). While Amanitales and Russulales tested were not found active, Polyporales and Boletales gave better results. Four species exhibited a significant cytotoxic activity (IC50 < or = 20 microg/ml) against at least one of the two murine cancer cell lines (Ganoderma lucidum, Meripilus giganteus, Suillus granulatus, S. luteus). The last one had never been investigated for its cytotoxic compounds before.
  Pharmazie 05/2004; 59(4):290-3. · 1.01 Impact Factor
• Article: Cytotoxic activity of some lichen extracts on murine and human cancer cell lines.

  C Bézivin, S Tomasi, F Lohézic-Le Dévéhat, J Boustie
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  ABSTRACT: Eight lichens were extracted successively with n-hexane, diethyl ether and methanol using a Soxhlet process. The cytotoxic activity of the 24 lichen extracts was evaluated in vitro using two murine (the L1210: lymphocytic leukaemia, and the 3LL: Lewis lung carcinoma) and four human (the K-562: chronic myelogenous leukaemia, the U251: glioblastoma, the DU145: prostate carcinoma, and the MCF7: breast adenocarcinoma) cancer cell lines and non-cancerous cells, the Vero cell line (African green monkey kidney cell line). The MTT assay revealed significant cytotoxicity (IC50 < or = 20 microg/ml) on one of the tested cancer cell lines for at least one extract of each lichen species. Some extracts of Cladonia convoluta, Cladonia rangiformis, Parmelia caperata, Platismatia glauca and Ramalina cuspidata demonstrated interesting activities particularly on human cancer cell lines as good selectivity indices were recorded (SI > 3).
  Phytomedicine 02/2003; 10(6-7):499-503. · 3.27 Impact Factor
• Article: A prenyloxycoumarin from Psiadia dentata.

  H Fortin, S Tomasi, P Jaccard, V Robin, J Boustie
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  ABSTRACT: A new coumarin identified as 5-hydroxy-6-methoxy-7-(3-methyl-but-2-enyloxy)-2H-1-benzopyran-2-one (isoobtusitin) was isolated from Psiadia dentata. This compound showed, in vitro, a moderate inhibitory activity against poliovirus and a very weak activity against (HIV), whereas it was inactive against (HSV1), (VSV), and murine tumoral cell lines (3LL, L1210).
  CHEMICAL & PHARMACEUTICAL BULLETIN 06/2001; 49(5):619-21. · 1.59 Impact Factor
• Article: NMR spectral data of salazinic acid isolated from some species of Parmotrema

  V. L. Eifler-Lima, A. Sperry, S. Sinbandhit, J. Boustie, S. Tomasi, E. Schenkel
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  ABSTRACT: In the investigation of lichens from the genus Parmotrema, P. tinctorum and P. delicatulum were examined. Salazinic acid was isolated as the main compound (ca 16%) from both species. Although this depsidone has already been reported for some species of this genus, this is the first report for P. tinctorum. The complete 1H and 13C NMR spectral assignments are reported. These assignments were confirmed by data obtained from HMQC and HMBC spectral analyses. Copyright © 2000 John Wiley & Sons, Ltd.
  Magnetic Resonance in Chemistry 06/2000; 38(6):472 - 474. · 1.44 Impact Factor
• Article: Solid phase organic synthesis of polyamine derivatives and initial biological evaluation of their antitumoral activity.

  S Tomasi, M Le Roch, J Renault, J C Corbel, P Uriac, B Carboni, D Moncoq, B Martin, J G Delcros
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  ABSTRACT: A series of N1-monosubstituted putrescine and spermine derivatives was synthesised using a solid phase methodology. We evaluated their cytotoxicity, calmodulin antagonism and polyamine uptake inhibition, pharmacological properties shared by some antitumoral agents.
  Bioorganic & Medicinal Chemistry Letters 04/1998; 8(6):635-40. · 2.55 Impact Factor
• Article: Inhibition of tumor growth and polyamine uptake by tetracyclic amidines bearing a putrescine moiety.

  T Mens, S Tomasi, V L Eifler-Lima, P Uriac, J Huet, V Catros-Quemener
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  ABSTRACT: Tetracyclic amidines (tetrahydroquino[4.3-b][l]benzazepine: compound 11 and tetrahydrobenzo[k]naphthyridine: compound 12) bearing a putrescine moiety possess significant DNA-binding affinity. We report here that these compounds and their a and b isomers inhibit tumor cell growth and putrescine uptake in 3LL carcinoma cells in vitro. Moreover, compound 11 reduced by 50% the accumulation of putrescine in intestinal brush border membrane vesicles. In CHO-MG, a cell line deficient for the specific polyamine uptake system, the cytotoxicity of these compounds was significantly reduced compared to the CHO wild cell line. The IC50 for CHO-MG was significantly higher than for CHO, demonstrating that the polyamine transport system increased the efficacy of these compounds. The efficacy of compounds 11 and 12 might therefore be related to their ability to interact with DNA as well as their structural analogy with polyamines. Moreover, we clearly show that DFMO enhances the efficacy of these tetracyclic amidines in vivo. Potential mechanisms include: a) lower intracellular polyamine levels reduces polyamine DNA-stabilizing functions, increasing accessibility for DNA-binding drugs; b) DFMO enhances the polyamine uptake system in tumor cells, increasing the entry of tetracyclic amidines bearing a putrescine moiety as well as their accessibility to final DNA-binding sites. The fact that natural polyamine uptake is reduced by the same compounds constitutes an additive mechanism for antitumoral efficiency.
  Anticancer research 17(6D):4327-32. · 1.73 Impact Factor