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Bioorg Chem. 2018 Apr;77:411-419. doi: 10.1016/j.bioorg.2018.01.021. Epub 2018 Jan 16.

New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors.

Author information

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, Turkey. Electronic address: incigul@atauni.edu.tr.
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, Turkey.
3
Meikai University Research Institute of Odontology (M-RIO), Sakado, Saitama 350-0283, Japan.
4
Neurofarba Department, Sezione di Scienza Farmaceutiche e Nutraceutiche, Universita degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.
5
Latvian Biomedical Research and Study Center, Ratsupites 1, Riga, Latvia.
6
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri 04100, Turkey.
7
Neurofarba Department, Sezione di Scienza Farmaceutiche e Nutraceutiche, Universita degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

In this study, new 4-[3-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (4-[5-(3,4,5-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA I/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA I/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates.

KEYWORDS:

Anticancer; Carbonic anhydrases; Dental cells; Pyrazoline; Sulfonamide

PMID:
29427856
DOI:
10.1016/j.bioorg.2018.01.021
[Indexed for MEDLINE]

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