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

Gonder

Journal of Enzyme Inhibition and Medicinal Chemistry

et al. 2019

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A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. K I values of these sulphonamides were in the range of 21 ± 4-72 ± 2 nM towards hCA I and in the range of 16 ± 6-40 ± 2 nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (K I s of 21 nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated.

Section: Carbonic Anhydrase Inhibition Assaymentioning

confidence: 99%

Novel sulphonamides incorporating triazene moieties show powerful carbonic anhydrase I and II inhibitory properties

Gonder

Journal of Enzyme Inhibition and Medicinal Chemistry

et al. 2019

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“…Therefore, the compounds were also evaluated against HGF and HPLF nonmalignant cells, as normal cells surround the tumor cells in an organism. Therefore, tumor selectivity (TS) values were calculated by dividing the average CC 50 value toward normal cells by the average CC 50 value toward cancer cell lines as reported [ 3,28,40,44,51,64,65 ] (Table 1). According to results, the TS values of all compounds were >1, which implies that they were all tumor‐selective compounds.…”

Section: Resultsmentioning

confidence: 99%

“…[ 27 ] The α,β‐unsaturated carbonyl system is responsible for the biological activities of the chalcones. [ 26,28 ] Various chalcone derivatives have been reported with many biological activities such as anti‐inflammatory, [ 29,30 ] antimicrobial, [ 31 ] antifungal, [ 32 ] antioxidant, [ 33 ] antimalarial, [ 34 ] antileishmanial, [ 35,36 ] anticancer, [ 37–39 ] cytotoxic, [ 40–42 ] CA inhibiting, [ 43–45 ] and anti‐invasive [ 46 ] activities.…”

Section: Introductionmentioning

confidence: 99%

New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6‐(3‐Halogenated phenyl‐2‐propen‐1‐oyl)‐2(3H)‐benzoxazolones

Erdal

et al. 2020

Archiv der Pharmazie

In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones (2a-n), were synthesized for the first time (except 2a), and their chemical structures were characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m, 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC 50 ) and potency selectivity expression (PSE) values. Thus, compound 2m can be considered as a lead compound of the series in terms of cytotoxicity. When the CA inhibition results of the compounds were evaluated, it was found that the K i values of the compounds ranged from 30.5 ± 11.3 to 65.5 ± 25.6 µM toward hCA I, and they ranged from 7.3 ± 1.8 to 58.8 ± 12.3 µM toward hCA II. However, the K i values of the reference drug, acetazolamide (AZA), were 30.2 ± 7.8 and 4.4 ± 0.6 μM toward hCA I and hCA II, respectively. According to the results obtained, compounds 2a-n had lower K i values than AZA, whereas compounds 2a, 2b, 2e-g, 2l, and 2n had similar K i values, compared with AZA. So, the compounds 2a, 2b, 2e-g, 2l, and 2n can be considered as lead molecules of this series for further considerations.

“…Chalcones are 1,3-diaryl-2-propen-1-ones, which consist of two aromatic rings connected by a three-carbons chain including a,b-unsaturated carbonyl system 12 . Depending on substitution on the aryl ring, chalcones have a wide range of biological activities such as antiinflammatory 13,14 , antimicrobial 15,16 , antioxidant 17 , cytotoxic/anticancer 18,19 , chemopreventive 20 , topoisomerase inhibiting 4 , carbonic anhydrase (CA) inhibiting 21,22 and acetylcholine esterase inhibiting activities 23 .…”

Section: Introductionmentioning

confidence: 99%

“…Antiglaucomal agents (CA II, IV, and XII), diuretics (CA II, IV, XII, and XIV), antiepileptics (CA VII, and XIV) inhibit several isoenzymes of CA. Some chalcone compounds have been reported as attractive scaffolds for the development of new CA inhibitors 21,41 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, cytotoxicities, and carbonic anhydrase inhibition potential of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones

Journal of Enzyme Inhibition and Medicinal Chemistry

Erdal

et al. 2019

Self Cite

In this study, new chalcone compounds having the chemical structure of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones (1-8) were synthesised and were characterised by 1 H-NMR, 13 C-NMR, and HRMS spectra. Cytotoxic and carbonic anhydrase (CA) inhibitory effects of the compounds were investigated. Cytotoxicity results pointed out that compound 4, 6-[3-(4-trifluoromethylphenyl)-2-propenoyl]-3H-benzoxazol-2-one, showed the highest cytotoxicity (CC 50) and potency-selectivity expression (PSE) value, and thus can be considered as a lead compound of this study. According to the CA inhibitory results, IC 50 values of the compounds 1-8 towards hCA I were in the range of 29.74-69.57 mM, while they were in the range of 18.14-48.46 mM towards hCA II isoenzyme. K i values of the compounds 1-8 towards hCA I were in the range of 28.37 ± 6.63-70.58 ± 6.67 mM towards hCA I isoenzyme and they were in the range of 10.85 ± 2.14-37.96 ± 2.36 mM towards hCA II isoenzyme.