Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII

Durgun, Mustafa; Türkmen, Hasan; Ceruso, Mariangela; Supuran, Claudiu T.

doi:10.1016/j.bmc.2016.01.020

Cited by 33 publications

(40 citation statements)

References 89 publications

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“…Schiff base derivatives are known for their important biological applications, especially as efficient and selective CAIs targeting several isozymes among which CA I, IV, and IX isozymes 38–41 , 49 , but they were not investigated so far as CAAs. This is the reason why the histamine Schiff base derivatives H(1–20) were obtained and assessed as activators of selected CA isoforms, involved in crucial physiologic and pathologic processes.…”

Section: Resultsmentioning

confidence: 99%

“…Schiff base derivatives of sulphonamides were extensively studied as an efficient and selective inhibitors of several CAs by us and other researchers 38–41 . However, a procedure successfully used to obtain sulphonamide CAIs incorporating Schiff base moieties, that is, reaction of amino sulphonamide with aldehydes to produce Schiff base derivatives, has never been approached for preparing histamine derivatives with potential CA activating properties.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators

Akocak

Lolak

Vullo

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure–activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators

Akocak

Lolak

Vullo

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…However, these derivatives also inhibited hCA I and hCA II effectively with low nanomolar range inhibitory action. 303 These compounds were ineffective against off-target cytosolic isoforms hCA I as well as hCA II, and displayed a K i value of >100 000 nM for both isoforms. 304 (Figure 20).…”

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confidence: 95%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

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163

166

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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“…The time and dose-dependent cytotoxic effects on cancer (HT-29, HeLa, MDA-MB-231) and normal cells (HEK-293 and PNT-1A) of synthesised seven sulphonamide derivatives determined with the feature of CA IX enzyme inhibitor in a study by Durgun et al. 16 , 17 were examined with the WST-1 method. The values of the compounds and 5-Fu IC 50 used as positive control are shown in Table 4 .…”

Section: Resultsmentioning

confidence: 99%

“…These CA inhibitors have been shown to induce a moderately effective, reversible inhibition of the membrane-bound isozyme CA IX compared with traditional inhibitors. The K i’s of the CA inhibitors and the chemical structures of the inhibitors tested are shown in Table 1 16 , 17 .…”

Section: Methodsmentioning

confidence: 99%

Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells

Koyuncu

Gönel

Koçyiğit

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Selective inhibition with sulphonamides of carbonic anhydrase (CA) IX reduces cell proliferation and induces apoptosis in human cancer cells. The effect on CA IX expression of seven previously synthesised sulphonamide inhibitors, with high affinity for CA IX, as well as their effect on the proliferation/apoptosis of cancer/normal cell lines was investigated. Two normal and three human cancer cell lines were used. Treatment resulted in dose- and time-dependent inhibition of the growth of various cancer cell lines. One compound showed remarkably high toxicity towards CA IX-positive HeLa cells. The mechanisms of apoptosis induction were determined with Annexin-V and AO/EB staining, cleaved caspases (caspase-3, caspase-8, caspase-9) and cleaved PARP activation, reactive oxygen species production (ROS), mitochondrial membrane potential (MMP), intracellular pH (pHi), extracellular pH (pHe), lactate level and cell cycle analysis. The autophagy induction mechanisms were also investigated. The modulation of apoptotic and autophagic genes (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin and LC3) was measured using real time PCR. The positive staining using γ-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-8, caspase-9, increased ROS production, MMP and enhanced mRNA expression of apoptotic genes, suggesting that anticancer effects are also exerted through its apoptosis-inducing properties. Our results show that such sulphonamides might have the potential as new leads for detailed investigations against CA IX-positive cervical cancers.

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Synthesis of 4-sulfamoylphenyl-benzylamine derivatives with inhibitory activity against human carbonic anhydrase isoforms I, II, IX and XII

Cited by 33 publications

References 89 publications

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Selective inhibition of carbonic anhydrase-IX by sulphonamide derivatives induces pH and reactive oxygen species-mediated apoptosis in cervical cancer HeLa cells

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