Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities
Özet
ABSTRACT
Thiadiazole and hydrazone derivatives (5a–5i) were synthesized
and their chemical structures were verified and described by
1
H NMR,
13
C NMR, and HRMS spectra. Three cancer cell lines
(MCF-7, MDA, and HT-29) and one healthy cell line (L929) were
used to test the cytotoxicity activity of synthesized compounds
as well as their inhibitory activity against carbonic anhydrase I,
II and IX isoenzymes. Compound 5d (29.74 µM) had a high
inhibitory effect on hCA I and compound 5b (23.18 µM) had
a high inhibitory effect on hCA II. Furthermore, compound 5i
was found to be the most potent against CA IX. Compounds 5a-
5i, 5b and 5i showed the highest anticancer effect against MCF-
7 cell line with an IC
value of 9.19 and 23.50 µM, and compound
5d showed the highest anticancer effect against MDA
cell line with an IC
50
50
value of 10.43 µM. The presence of fluoro
substituent in the o-position of the phenyl ring increases the
effect on hCA II, while the methoxy group in the o-position of
the phenyl ring increases the activity on hCA I as well as
increase the anticancer activity. Cell death induction was eval-
uated by Annexin V assay and it was determined that these
compounds cause cell death by apoptosis. Molecular docking
was performed for compounds 5b and 5d to understand their
biological interactions. The physical and ADME properties of
compounds 5b and 5d were evaluated using SwissADME.