Synthesis, Anticancer Activity and Carbonic Anhydrase Inhibitory Activity of new Thiadiazole-hydrazone Derivatives
Abstract
In five steps, new compounds 5a, 5b of thiadiazole-hydrazone derivatives were synthesized. Various spectral methods, such as 1H NMR, 13C NMR, and elemental analyses, were used to clarify the structures of the compounds. Three cancer cell lines (MCF7, MDA, and HT-29) and one healthy cell line (L929) were tested for the cytotoxicity activity of synthetic compounds, as well as their inhibitory action against carbonic anhydrase I and II isoenzymes (hCA I and hCA II). Among them, the compound 5b exhibited remarkable CA inhibitory activities compared to a standard inhibitor with IC50 values at of 27 µM for hCA I and 33,46 µM for hCA II. The compounds have been found to be ineffective against cancer cell lines. Furthermore, the compounds were found to be non-toxic to the healthy cell line.
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References
- [1] Tapera M., Kekeçmuhammed H., Tüzün B., Sarıpınar E., Koçyiğit Ü. M., Yıldırım E., Doğen M., Zorlu Y., Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular docking studies of new imidazolyl hydrazone derivatives, J. Mol. Struct., 1269 (2022) 133816.
- [2] Bilginer S., Bardaweel S. K., Demir Y., Gulcin I., & Kazaz C., Synthesis, cytotoxicities, and carbonic anhydrase inhibition activities of pyrazoline–benzenesulfonamide derivatives harboring phenol/polyphenol moieties, Med. Chem. Res., (2022) 1-11.
- [3] Bonardi A., Bua S., Combs J., Lomelino C., Andring J., Osman S. M., Toti A., Mannelli L.D.C., Gratteri P., Ghelardini C., McKennac R., Nocentini A., The three-tails approach as a new strategy to improve selectivity of action of sulphonamide inhibitors against tumour-associated carbonic anhydrase IX and XII, J. Enzyme Inhib. Med. Chem., 37(2022) 930-939.
- [4] Arrighi G., Puerta A., Petrini A., Hicke F. J., Nocentini A., Fernandes M. X., Padron J.M., Supuran C.T., Fernandes-Bolanos J.M., López Ó., Squaramide-Tethered Sulfonamides and Coumarins: Synthesis, Inhibition of Tumor-Associated CAs IX and XII and Docking Simulations, Int. J. Mol. Sci., 23 (2022) 7685.
- [5] Tawfik H. O., Petreni A., Supuran C. T., & El-Hamamsy M. H., Discovery of new carbonic anhydrase IX inhibitors as anticancer agents by toning the hydrophobic and hydrophilic rims of the active site to encounter the dual-tail approach, Eur. J. Med. Chem., 232 (2022) 114190.
- [6] Al-Warhi T., Elbadawi M. M., Bonardi A., Nocentini A., Al-Karmalawy A. A., Aljaeed N., Alotaibi O.J., Abdel-Aziz H.A., Supuran C.T., Eldehna W. M., Design and synthesis of benzothiazole-based SLC-0111 analogues as new inhibitors for the cancer-associated carbonic anhydrase isoforms IX and XII, J. Enzyme inhib. Med. Chem., 37(2022) 2635-2643.
- [7] Elimam D. M., Eldehna W. M., Salem R., Bonardi A., Nocentini A., Al-Rashood S. T., Elaasser M.M., Gratteri P., Supuran C.T., Allam H. A., Natural inspired ligustrazine-based SLC-0111 analogues as novel carbonic anhydrase inhibitors, Eur. J. Med. Chem., 228 (2022) 114008.
- [8] Vanjare B. D., Choi N. G., Eom Y. S., Raza H., Hassan M., Lee K. H., & Kim S. J., Synthesis, carbonic anhydrase inhibition, anticancer activity, and molecular docking studies of 1, 3, 4-oxadiazole derivatives, Mol. Diver. (2022) 1-16.
- [9] Hagras M., Saleh M. A., Ezz Eldin R. R., Abuelkhir A. A., Khidr E. G., El-Husseiny A. A., El-Mahdy H.A., Elkaeed E.B., Eissa I. H., 1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and in silico studies. J. Enzyme inhib. Med. Chem., 37 (2022) 386-402.
- [10] Abdelgawad M. A., Bukhari S. N., Musa A., Elmowafy M., Elkomy M. H., Nayl A. A., ... & Elshemy, H. A., New Sulfamethoxazole Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors: Design, Synthesis, Cytotoxic Activity and Molecular Modeling, Pharmaceuticals., 15 (2022) 1134.