Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3

Silvia Dell'Orto, Daniela Masciocchi, Stefania Villa, Fiorella Meneghetti, Giuseppe Celentano, Daniela Barlocco, Diego Colombo, Laura Legnani, Lucio Toma, Yoon Jung Jeon, Byoung Mog Kwon, Akira Asai, Arianna Gelain

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Signal Transducer and Activator of Transcription 3 (STAT3) is a cytoplasmic factor that mediates intracellular signaling commonly generated at cell surface receptors and transmits it to the nucleus. In previous research studies we synthesized several molecules inhibiting STAT3 and among them oxadiazole MD77 and pyridazinone I showed an interesting activity. For the first one, a direct inhibition mechanism was determined, while I interfered within the STAT3 pathway at a different level. In order to discover novel compounds possibly endowed with an improved activity, we decided to merge their scaffolds on the basis of their calculated conformational properties. Therefore we designed and synthesized the chimera diastereomers 3-oxo-N-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydrobenzo[h]cinnoline-6-carboxamide (1, 2) and 3-oxo-N-(4-(trifluoromethyl)phenyl)-2,3,5,6-tetrahydrobenzo[h]cinnoline-6-carboxamide (3) as racemate and their enantiomeric separation was performed. Modeling studies and theoretical prediction of [α]D values were carried out beside NMR studies which allowed us to assign 1 and 2 relative configurations.

Original languageEnglish
Pages (from-to)1651-1657
Number of pages7
JournalMedChemComm
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

STAT3 Transcription Factor
Nuclear magnetic resonance
Oxadiazoles
Cell Surface Receptors
Scaffolds
Theoretical Models
Molecules
Research
cinnoline

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

Dell'Orto, S., Masciocchi, D., Villa, S., Meneghetti, F., Celentano, G., Barlocco, D., ... Gelain, A. (2014). Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3. MedChemComm, 5(11), 1651-1657. https://doi.org/10.1039/c4md00177j

Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3. / Dell'Orto, Silvia; Masciocchi, Daniela; Villa, Stefania; Meneghetti, Fiorella; Celentano, Giuseppe; Barlocco, Daniela; Colombo, Diego; Legnani, Laura; Toma, Lucio; Jeon, Yoon Jung; Kwon, Byoung Mog; Asai, Akira; Gelain, Arianna.

In: MedChemComm, Vol. 5, No. 11, 01.11.2014, p. 1651-1657.

Research output: Contribution to journalArticle

Dell'Orto, S, Masciocchi, D, Villa, S, Meneghetti, F, Celentano, G, Barlocco, D, Colombo, D, Legnani, L, Toma, L, Jeon, YJ, Kwon, BM, Asai, A & Gelain, A 2014, 'Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3', MedChemComm, vol. 5, no. 11, pp. 1651-1657. https://doi.org/10.1039/c4md00177j
Dell'Orto S, Masciocchi D, Villa S, Meneghetti F, Celentano G, Barlocco D et al. Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3. MedChemComm. 2014 Nov 1;5(11):1651-1657. https://doi.org/10.1039/c4md00177j
Dell'Orto, Silvia ; Masciocchi, Daniela ; Villa, Stefania ; Meneghetti, Fiorella ; Celentano, Giuseppe ; Barlocco, Daniela ; Colombo, Diego ; Legnani, Laura ; Toma, Lucio ; Jeon, Yoon Jung ; Kwon, Byoung Mog ; Asai, Akira ; Gelain, Arianna. / Modeling, synthesis and NMR characterization of novel chimera compounds targeting STAT3. In: MedChemComm. 2014 ; Vol. 5, No. 11. pp. 1651-1657.
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