Synthesis of Novel Tryptamine Derivatives and Their Biological Activity as Antitumor Agents

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 M). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 M) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 M)

Synthesis and analysis of benzisoxazoles as substrates for the Kemp elimination in presence of hemoproteins

This elaborate focuses on the synthesis and kinetic analysis of substituted benzisoxazoles as substrates for the Kemp reaction, in presence of three hemoproteins, i.e. cytochrome c, myoglobin and hemoglobin. Formylation of a phenol derivative, nucleophilic addition of hydroxylamine and a final ciclization are the three step keys which afforded the desired fused isoxazole rings. The base-catalyzed decomposition of synthesized substrates was monitored through UV/Vis spectrophotometry, in order to study the catalytic effect of different enzymes under examination, using a common spectrophotometer UV/Vis. Finally the kinetic isotope effect of a deuterated substrate was analyzed to evidence the nature of the rate-limiting step of Kemp elimination

Novel hydroxystearoyl-, heterocyclic and carbocyclic derivatives: synthesis and applications in biological field

This PhD project has been mainly focused on the synthesis of novel organic compounds containing heterocyclic and/or carbocyclic scaffold and on the study of stearic acid derivatives and their applications in biological field. The synthesis of novel derivatives of 9-hydroxystearic acid (9-HSA) evidenced how the presence of substituents on C9, able to make hydrogen bonds is of crucial importance for the biological activity. Also the position of the hydroxy group along the chain of hydroxystearic acids was investigated: regioisomers with the hydroxy group bound to odd carbons resulted more active than those bearing the hydroxy group on even carbons. Further, the insertion of (R)-9-HSA in magnetic nanoparticles gave a novel material which characterization remarked its suitability for drug delivery. Structural hybrids between amino aza-heterocycles and azelaic acid have been synthesized and some of them showed a selective activity towards osteosarcoma cell line U2OS. Several Apcin analogues bearing indole, benzothiazole, benzofurazan moieties connected to tryptaminyl-, amino pyridinyl-, pyrimidinyl- and pyrazinyl ring through a 1,1,1-trichloroethyl group were synthesized. Biological tests showed the importance of both the tryptaminyl and the pyrimidinyl moieties, confirming the effectiveness against acute leukemia models. The SNAr between 2-aminothiazole derivatives and 7-chlorodinitrobenzofuroxan revealed different behaviour depending from amino substituent of the thiazole. The reaction with 2-N-piperidinyl-, 2-N-morpholinyl-, or 2-N-pyrrolidinyl thiazole gave two isomeric species derived from the attack on C-5 of thiazole ring. Thiazoles substituted with primary- or not-cyclic secondary amines reacted with the exocyclic amino nitrogen atom giving a series of compounds whose biological activity have highlighted as they might be promising candidates for further development of antitumor agents. A series of 9-fluorenylidene derivatives, of interest in medical and optoelectronic field as organic scintillators, was synthesized through Wittig or Suzuky reaction and will be analyzed to test their potential scintillatory properties

3,5-Dimethoxy-2-[(4-methoxyphenyl)diazenyl]phenol

3,5-Dimethoxy-2-[(4-methoxyphenyl)diazenyl]phenol was synthesized by an azo-coupling reaction between 3,5-dimethoxyphenol and 4-methoxy benzenediazonium tetrafluoroborate. The structure of newly synthesized compound was elucidated based on 1H NMR, 13C NMR, ESI-MS, UV-Vis and FT-IR

4,6-Dinitro-7-(thiazol-2-ylamino)benzo[c][1,2,5]oxadiazole 1-oxide

4,6-Dinitro-7-(thiazol-2-ylamino)benzo[c][1,2,5]oxadiazole 1-oxide was synthesized by a SNAr reaction between 7-chloro-4,6-dinitrobenzofuroxan and 2-aminothiazole. The structure of the newly synthesized compound (45% yield) was elucidated based on 1H-NMR, 13C-NMR, NOESY-1D, ESI-MS, UV-Vis, and FT-IR techniques

1,1’,1’’-(2’,4’-Dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine

The compound 1,1’,1’’-(2’,4’-dinitro-[1,1’-biphenyl]-2,4,6-triyl)tripiperidine was synthesized by SEAr/SNAr reaction between 1-fluoro-2,4-dinitrobenzene and 1,3,5-tris(N-piperidinyl)benzene. The structure of the newly synthesized compound was elucidated based on 1H-NMR, 13C-NMR, ESI-MS, UV-Vis and IR spectroscopy