Abstract
The starting precursors 2-carbohydrazides, bearing thienopyridine moiety, were prepared using 2-thioxopyridine-3-carbonitriles as key synthons. Next, 2-carbohydrazides were reacted with a variety of 4-substituted benzylidinemalononitriles or 4-substituted benzaldehydes to afford a new series of the target hydrazones incorporating thienopyridine moiety. The elemental analyses and spectral data were used to demonstrate the structures of new hydrazones series. The in vitro antibacterial activities of the target hydrazones were evaluated against different strains of Gram-positive and Gram-negative bacteria. In comparison with chloramphenicol as a reference drug, hydrazones
13b
,
13c
and
13d
, linked to
p
-Cl,
p
-Br and
p
-Me moiety, respectively, exhibited the strongest activities against all tested bacteria with MIC values in the range of 6.2–12.5 μg/mL. In addition, several new hydrazones were tested as in vitro cytotoxic agents against each of human breast carcinoma MCF-7 cell line, colon cancer Caco2 cell line and liver hepatocellular carcinoma HEPG2 cell line. The hydrazones
13b
,
13c
and
13d
demonstrated the best cytotoxicity against the tested eukaryotic cells. Furthermore, both experimental and docking studies could predict the promising inhibitory activities of hydrazones
13c
and
13d
against COX-2 enzyme with IC
50
of 0.110 and 0.104 µM, respectively, when compared with Celecoxib (IC
50
of 0.115 µM).
Graphic abstract