Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities

ABSTRACT

Thiadiazole and hydrazone derivatives (5a–5i) were synthesized and their chemical structures were verified and described by ¹H NMR, ¹³C 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 IC₅₀ value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC₅₀ 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 evaluated 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.

KEYWORDS:

• Thiadiazole
• hydrazone
• carbonic anhydrase
• anticancer
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2023.2240698

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.