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Journal of Enzyme Inhibition and Medicinal Chemistry Volume 32, 2017 - Issue 1
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Research Paper

New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors

Elena GabrieleDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy; View further author information
,
Dario BrambillaDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy; View further author information
,
Chiara RicciDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy; View further author information
,
Luca RegazzoniDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy; View further author information
,
Kyoko TaguchiCenter for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; View further author information
,
Nicola FerriDepartment of Pharmaceutical and Pharmacological Sciences, Università degli Studi di Padova, Largo Egidio Meneghetti, Padova, ItalyORCID Iconhttp://orcid.org/0000-0001-8898-7441View further author information
ORCID Icon,
Akira AsaiCenter for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; View further author information
&
Anna SparatoreDepartment of Pharmaceutical Sciences, Università degli Studi di Milano, Milano, Italy; Correspondence[email protected]
ORCID Iconhttp://orcid.org/0000-0003-2135-2649View further author information
ORCID Icon show all
Pages 1012-1028 | Received 11 May 2017, Accepted 30 Jun 2017, Published online: 25 Jul 2017

Figures & data

Figure 1. Structures of compounds a–i.

Figure 1. Structures of compounds a–i.

Figure 2. Structures of the investigated sulfurated moieties.

Figure 2. Structures of the investigated sulfurated moieties.

Figure 3. Structures of the investigated derivatives of ferulic, caffeic, and other cinnamic acids and of rosmaricine.

Figure 3. Structures of the investigated derivatives of ferulic, caffeic, and other cinnamic acids and of rosmaricine.

Scheme 1. Reagents and conditions: (a) DMF, N2, 60 °C, 5 h; (b) DMSO, N2, 60 °C, 5 h; (c) dry DMF, 60 °C, 5 h.

Scheme 1. Reagents and conditions: (a) DMF, N2, 60 °C, 5 h; (b) DMSO, N2, 60 °C, 5 h; (c) dry DMF, 60 °C, 5 h.

Scheme 2. Reagents and conditions: (a) MEM-Cl, DIPEA, anh. CH2Cl2, 5 h, 0 °C to r.t.; (b) LiOH*H2O, THF/H2O (2:1), 24 h, r.t.; (c) RH (1–5), DCC (EDAC for 38), DMAP, anh. CH2Cl2 (CHCl3 for 38), 3–20 h, r.t.; (d) TFA, anh. CH2Cl2, 4–7 h, r.t.

Scheme 2. Reagents and conditions: (a) MEM-Cl, DIPEA, anh. CH2Cl2, 5 h, 0 °C to r.t.; (b) LiOH*H2O, THF/H2O (2:1), 24 h, r.t.; (c) RH (1–5), DCC (EDAC for 38), DMAP, anh. CH2Cl2 (CHCl3 for 38), 3–20 h, r.t.; (d) TFA, anh. CH2Cl2, 4–7 h, r.t.

Scheme 3. Reagents and conditions: (a) H2SO4 (cat.), MeOH, reflux, 2 h; (b) NaH, MEM-Cl, anh. THF, 0 °C, 5 h; (c) 5 N NaOH, THF/MeOH (4:1), 40 °C, 3 h; (d) RH (1, 3–5), DCC or EDAC (for 29), DMAP, anh. THF or CH2Cl2 or CHCl3, 4–20 h, r.t.; (e) TFA, anh. CH2Cl2 or CHCl3, 5–8 h, r.t.

Scheme 3. Reagents and conditions: (a) H2SO4 (cat.), MeOH, reflux, 2 h; (b) NaH, MEM-Cl, anh. THF, 0 °C, 5 h; (c) 5 N NaOH, THF/MeOH (4:1), 40 °C, 3 h; (d) RH (1, 3–5), DCC or EDAC (for 29), DMAP, anh. THF or CH2Cl2 or CHCl3, 4–20 h, r.t.; (e) TFA, anh. CH2Cl2 or CHCl3, 5–8 h, r.t.

Scheme 4. Reagents and conditions: (a) DCC, DMAP, anh. CH2Cl2 or THF, r.t., 1–4 h.

Scheme 4. Reagents and conditions: (a) DCC, DMAP, anh. CH2Cl2 or THF, r.t., 1–4 h.

Scheme 5. Reagents and conditions: (a) ROH (6, 9, 11), EDAC, HOBt, DIPEA, anh. DMF, r.t., 2–6 h.

Scheme 5. Reagents and conditions: (a) ROH (6, 9, 11), EDAC, HOBt, DIPEA, anh. DMF, r.t., 2–6 h.

Figure 4. Structure of compound 45.

Figure 4. Structure of compound 45.

Table 1. Biological activities of sulfurated parent compounds (1–6, 9, and 11) and some related compounds (7, 8, and 10).

Table 2. Biological activities of parent compounds (ferulic acid 12, caffeic acid 19, and rosmaricine) and their sulfurated derivatives.

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