Akademik Veri Yönetim Sistemi
JOURNAL OF MOLECULAR STRUCTURE, cilt.1316, 2024 (SCI-Expanded)
Within the scope of this study, the design and synthesis of new triazole and oxadiazole compounds containing piperidine ring were carried out. The anticancer effects of the obtained compounds have been tested on lung and colon cancers. Especially in colon cancer, compounds 4Id, 4Ie, 4If and 4Ih exhibited significant activity profiles. Compounds 4Id, 4Ie, 4If and 4Ih showed activity against HT-29 cell line with IC50=19.238 +/- 0.652 mu M, 14.861 +/- 0.409 mu M, 20.876 +/- 0.374 mu M and 16.132 +/- 0.787 mu M, respectively. Compound 4Ie has an IC50 value greater than 100 mu M against healthy cells (NIH3T3). While this compound (4Ie) effectively eliminates colon cancer cells, it exhibits a lower tendency to harm healthy cells. Since the importance of VEGFR-2 inhibition in colon cancer, the active compounds were evaluated by means of in vitro enzyme inhibition test. Compounds 4Id, 4Ie, 4If and 4Ih showed activity against VEGFR-2 enzyme with IC50=0.105 +/- 0.002 mu M; 0.055 +/- 0.003 mu M; 1.096 +/- 0.005 mu M; 0.159 +/- 0.002 mu M; 0.039 +/- 0.001 mu M respectively. As a result of molecular docking and dynamics studies, it is seen that the stability of all compounds is excellent. However, especially compound 4Ie exhibited a strong inhibitory potential with its continuous interactions with Cys919, Glu885 and Asp1046. Dynamic investigations reveal the enzyme's stability within the active site, with particular emphasis on the cyano group's capability to engage with Cys919, rendering this compound the most potent derivative.