New Hybrids with 2-aminobenzothiazole and Azelayl Scaffolds: Synthesis, Molecular Docking and Biological Evaluation

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

“…Conversely, solid tumor models displayed a specific vulnerability towards compound 14 (the acid free form of the ester of compound 13 ), that was not effective against hematological cell lines. Of note, compounds 13 and 14 were both active against HT29 cells, in line with previous observations on similar compounds [ 17 ]. Moreover, these compounds recall the structure of HDAC inhibitors, that showed modest efficacy as single agent in acute leukemias [ 35 , 36 ].…”

“…Based on literature reports on the biological activity of compounds bearing different heterocyclic moieties bound to an azelayl chain through an amide bond [ 17 , 18 ], we planned to synthesize compounds 13 and 14 , bearing a tryptamine group.…”

“…were measured on a Büchi 535 apparatus (Büchi, Flawil, Switzerland) and are uncorrected. Methyl 9-Chloro-9-oxononanoate ( 12 ) was prepared as previously described [ 17 , 18 ]. GC-MS analyses were recorded with a Agilent 6890 Series (Agilent, Santa Clara, CA, USA) gas chromatograph interfaced with a Agilent 5973 Network quadrupole mass selective detector (injection temperature: 250 °C; oven temperature was programmed as follows: 60 °C for 2 min, increased up to 260 °C at the rate of 20°/min, followed by 260 °C for 20 min; the carrier gas was helium, used at a flow rate of 1 mL/min; the transfer line temperature was 280 °C; the ionization was obtained by electron impact (EI); the acquisition range was 50–500 m / z ).…”

“…Tryptamine (compound 1 , 320.5 mg, 2 mmol) was added to a magnetically stirred solution of crude freshly prepared compound 12 (1 mmol) [ 17 , 18 ]. After 3 h at room temperature, 1 H-NMR analysis of a sample revealed disappearance of the signals belonging to 12 .…”

“…The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as the molecular target [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Actually, we found that some derivatives belonging to series in Figure 2 B–D behave as selective histone deacetylase inhibitors (HDACi): benzothiazole-based series ( Figure 2 B) is active against HT29 human colon cancer cells line [ 17 ] whereas, among the series containing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups ( Figure 2 C,D), two aminopyrimidinyl and the benzimidazolyl derivatives showed specific activity on osteosarcoma cells [ 18 ]. The two latter moieties, aminopyrimidyl- and imidazolyl- one are also present in Apcin, ( Figure 2 E) a small molecule that blocks the interaction between APC/C and Cdc20 [ 19 ].…”