Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases

Karalı, Nilgün; Akdemir, Atilla; Göktaş, Füsun; Elma, Pınar Eraslan; Angeli, Andrea; Kızılırmak, Merih

doi:10.1016/j.bmc.2017.05.029

Cited by 27 publications

(20 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For all compounds, the multiplets observed between 8.06 and 6.63 ppm were assigned to the hydrogen atoms of the C 6 H 4 ring. As per literature reports, the broad singlet observed at 7.52–6.91 ppm was assigned to the hydrogen nuclei of the SO 2 NH 2 group 18 , 30 , 31 .…”

Section: Resultssupporting

confidence: 76%

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases

Huentupil

Peña

Novoa

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

A series of organometallic acylhydrazones was prepared, incorporating Re(CO)3, Mn(CO)3 and ferrocenyl moieties, which were subsequently reacted with amino-sulfonamides in order to obtain carbonic anhydrase (CA, EC 4.2.1.1) inhibitors possessing organometallic moieties in their molecules. The new derivatives were investigated as inhibitors of four human (h) CA isoforms with pharmaceutical applications, such as the cytosolic hCA I, II and VII and the mitochondrial hCA VA. An interesting inhibitory profile against these isoforms was obtained, with some of these metal complexes acting as subnanomolar or low nanomolar inhibitors. They were also thoroughly characterised from the chemical point of view, making them of interest for further developments in the field of metal complexes of sulfonamides with CA inhibitory action.

show abstract

Section: Resultssupporting

confidence: 76%

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases

Huentupil

Peña

Novoa

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The examined ferrocene-containing camphor sulfonamides DK-164 and CC-78 demonstrated different cytotoxic selectivity toward lung cancer cell lines A549 and H1299 compared to the non-cancerous MRC5. In concern with selectivity, molecular docking studies have been made with many sulfonamide derivatives [ 23 ]. It was shown that the sulfonamide tail of the active compounds could interact with Zn 2+ in the active site of the enzyme carbonic anhydrase IX/XII, suggesting the importance of the sulfonamide moiety in inhibiting its action [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells

et al. 2022

View full text Add to dashboard Cite

The successful design of antitumour drugs often combines in one molecule different biologically active subunits that can affect various regulatory pathways in the cell and thus achieve higher efficacy. Two ferrocene derivatives, DK-164 and CC-78, with different residues were tested for cytotoxic potential on non-small lung cancer cell lines, A549 and H1299, and non-cancerous MRC5. DK-164 demonstrated remarkable selectivity toward cancer cells and more pronounced cytotoxicity against A549. The cytotoxicity of CC-78 toward H1299 was even higher than that of the well-established anticancer drugs cisplatin and tamoxifen, but it did not reveal any noticeable selective effect. DK-164 showed predominantly pro-apoptotic activity in non-small cell lung carcinoma (NSCLC) cells, while CC-78 caused accidental cell death with features characteristic of necrosis. The level of induced autophagy was similar for both substances in cancer cells. DK-164 treatment of A549, H1299, and MRC5 cells for 48 h significantly increased the fluorescence signal of the NFkB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) protein in the nucleus in all three cell lines, while CC-78 did not provoke NFkB translocation in any of the tested cell lines. Both compounds caused a significant transfer of the p53 protein in the nucleus of A549 cells but not in non-cancerous MRC5 cells. In A549, DK-164 generated oxidative stress close to the positive control after 48 h, while CC-78 had a moderate effect on the cellular redox status. In the non-cancerous cells, MRC5, both compounds produced ROS similar to the positive control for the same incubation period. The different results related to the cytotoxic potential of DK-164 and CC-78 associated with the examined cellular mechanisms induced in lung cancer cells might be used to conclude the specific functions of the various functional groups in the ferrocene compounds, which can offer new perspectives for the design of antitumour drugs.

show abstract

“…In a recent study, we described the synthesis of novel 1 H -indole-2,3-dione 3-thiosemicarbazone derivatives (compounds 4a – m ) carrying a sulfamoyl group at 4-position of the phenyl ring, molecular modeling studies for target enzymes and the effects of the synthesised compounds on tumor-associated hCA IX and XII enzymes 39 . All of the tested compounds showed selective inhibition in the low nanomolar range for hCA IX and XII enzymes over cytosolic isoforms hCA I and II enzymes.…”

Section: Introductionmentioning

confidence: 99%

Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme

Akdemir

Angeli

Göktaş

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1 H -indole-2,3-dione 3-[ N -(4-sulfamoylphenyl)thiosemicarbazones] 4a–m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (K I of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies.

show abstract

Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrases

Cited by 27 publications

References 29 publications

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases

In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells

Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme

Contact Info

Product

Resources

About