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4‐Diazo and 4‐(Triaz‐1‐en‐1‐yl)‐1 H ‐pyrrole‐2‐carboxylates as Agents Inducing Apoptosis
Author(s) -
Galenko Ekaterina E.,
Galenko Alexey V.,
Novikov Mikhail S.,
Khlebnikov Alexander F.,
Kudryavtsev Igor V.,
Terpilowski Maxim A.,
Serebriakova Maria K.,
Trulioff Andrey S.,
Goncharov Nikolay V.
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201701538
Subject(s) - pyrrole , apoptosis , diazo , chemistry , cytotoxic t cell , pyridinium , carboxylate , stereochemistry , cell culture , medicinal chemistry , in vitro , biochemistry , organic chemistry , biology , genetics
New β‐diazopyrrole and β‐triazenylpyrrole derivatives were synthesized from isoxazoles and pyridinium salts in two and three steps, respectively. The apoptotic/necrotic difference for these compounds was estimated on THP‐1 cell line. The most effective of the panel is methyl 3‐diazo‐2‐(2,4‐dimethylphenyl)‐4‐phenyl‐3 H ‐pyrrole‐5‐carboxylate which demonstrated cytotoxic activity from the lowest concentration of 3.3 μM with a steep rise of the apoptotic effect and the largest apoptotic/necrotic difference within the range of 3.3 to 33 μM. Moreover, this diazopyrrole showed the highest sum total of apoptotic and necrotic AUCs within the same low range of concentrations. Methyl 2‐(4‐bromophenyl)‐3‐diazo‐4‐(3‐methoxyphenyl)‐3 H ‐pyrrole‐5‐carboxylate and methyl 5‐(4‐bromophenyl)‐3‐(3‐methoxyphenyl)‐4‐(piperidin‐1‐yl/morpholin‐4‐yldiazenyl)‐1 H ‐pyrrole‐2‐carboxylates were found to be quite promising compounds which deserve further cytophysiological and mechanistic research using different cell lines.