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Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes.
Bioorg Chem. 2018 08; 78:290-297.BC

Abstract

In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively.

Authors+Show Affiliations

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey. Electronic address: incigul1967@yahoo.com.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir, Turkey.Department of Physiology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29621641

Citation

Gul, Halise Inci, et al. "Anticancer Effects of New Dibenzenesulfonamides By Inducing Apoptosis and Autophagy Pathways and Their Carbonic Anhydrase Inhibitory Effects On hCA I, hCA II, hCA IX, hCA XII Isoenzymes." Bioorganic Chemistry, vol. 78, 2018, pp. 290-297.
Gul HI, Yamali C, Bulbuller M, et al. Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes. Bioorg Chem. 2018;78:290-297.
Gul, H. I., Yamali, C., Bulbuller, M., Kirmizibayrak, P. B., Gul, M., Angeli, A., Bua, S., & Supuran, C. T. (2018). Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes. Bioorganic Chemistry, 78, 290-297. https://doi.org/10.1016/j.bioorg.2018.03.027
Gul HI, et al. Anticancer Effects of New Dibenzenesulfonamides By Inducing Apoptosis and Autophagy Pathways and Their Carbonic Anhydrase Inhibitory Effects On hCA I, hCA II, hCA IX, hCA XII Isoenzymes. Bioorg Chem. 2018;78:290-297. PubMed PMID: 29621641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anticancer effects of new dibenzenesulfonamides by inducing apoptosis and autophagy pathways and their carbonic anhydrase inhibitory effects on hCA I, hCA II, hCA IX, hCA XII isoenzymes. AU - Gul,Halise Inci, AU - Yamali,Cem, AU - Bulbuller,Merve, AU - Kirmizibayrak,Petek Ballar, AU - Gul,Mustafa, AU - Angeli,Andrea, AU - Bua,Silvia, AU - Supuran,Claudiu T, Y1 - 2018/03/30/ PY - 2018/02/17/received PY - 2018/03/29/revised PY - 2018/03/29/accepted PY - 2018/4/6/pubmed PY - 2019/1/29/medline PY - 2018/4/6/entrez KW - Anticancer KW - Apoptosis KW - Autophagy KW - Carbonic anhydrase KW - Pyrazole KW - Sulfonamide SP - 290 EP - 297 JF - Bioorganic chemistry JO - Bioorg Chem VL - 78 N2 - In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory effects of the dibenzensulfonamides 7-9 were also evaluated on the cytosolic human (h) hCA I and II and the tumor-associated hCA IX and XII isoenzymes. Results indicate that both 7 and 8 induced cleavage of poly (ADP ribose) polymerase (PARP), activation of caspases -3, -7 and -9 which are the hallmarks of apoptosis. Meanwhile both compounds induced autophagy in HCC1937 cells which is shown by enhanced expression of LC3 and decreased level of p62 protein. The compounds tested were also effectively inhibited tumor-associated hCA IX and hCA XII isoenzymes in the range of 20.7-28.1 nM and 4.5-9.3 nM, respectively. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/29621641/Anticancer_effects_of_new_dibenzenesulfonamides_by_inducing_apoptosis_and_autophagy_pathways_and_their_carbonic_anhydrase_inhibitory_effects_on_hCA_I_hCA_II_hCA_IX_hCA_XII_isoenzymes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)30155-X DB - PRIME DP - Unbound Medicine ER -