Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines

Krasavin, Mikhail; Shetnev, Аnton; Baykov, Sergey V.; Kalinin, Stanislav; Nocentini, Alessio; Sharoyko, Vladimir V.; Poli, Giulio; Tuccinardi, Tiziano; Korsakov, Mikhail; Tennikova, Tatiana; Supuran, Claudiu T.

doi:10.1016/j.ejmech.2019.02.044

Cited by 28 publications

(20 citation statements)

References 46 publications

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“…While being comparable to these syntheses in terms of the number of steps, our approach involves a mild Rh II ‐catalyzed N–H carbene insertion step and is likely to display a different functional group tolerance profile. Furthermore, the presence of a primary sulfonamide group in compound 3p makes it a potential carbonic anhydrase inhibitor . As already noted above, the active chlorine in compound 3t could be easily substituted by different amines thus delivering the ubiquitous bioactive 2,4‐diaminopyrimidine scaffold , …”

Section: Resultsmentioning

confidence: 94%

Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

2019

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Decomposition of α‐diazo‐γ‐butyrolactams in the presence of aromatic and heteroaromatic amines, under Rh2(esp)2 catalysis, led to corresponding α‐arylamino‐γ‐butyrolactams, which are of significant value for medicinal chemistry. The reaction scope encompasses primary as well as secondary, diversely substituted anilines and heteroaromatic amines. Insertion into the anilinic amino group was shown to be selective over amide and sulfonamide N–H insertion.

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Section: Resultsmentioning

confidence: 94%

Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

2019

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“…To our delight, however, there is a large number of mechanistically relevant experiments reported in the literature which address the ability of hCA IX/XII inhibitors to block the growth of hypoxic cancer cells overexpressing the target isozymes [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] . Moreover, a certain cohort of studies revealed compounds possessing both favourable hCA inhibitory profile and significant anticancer activity, as exemplified by structures 5-13 ( Figure 2) [49][50][51][52][53][54][55][56][58][59][60][61][64][65][66][67] . In fact, quite a number of single-digit nanomolar hCA IX/XII inhibitors significantly suppressed cancer cell growth.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

Krasavin

Kalinin

Sharonova

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Analysis of the literature data reveals that while inhibition of cancer-related carbonic anhydrase IX and XII isoforms continues to be an important enrichment factor for designing anticancer agent development libraries, exclusive reliance on the in vitro inhibition of these two recombinant isozymes in nominating candidate compounds for evaluation of their effects on cancer cells may lead not only to identifying numerous compounds devoid of the desired cellular efficacy but also to overlooking many promising candidates which may not display the best potency in biochemical inhibition assay. However, SLC-0111, now in phase Ib/II clinical trials, was developed based on the excellent agreement between the in vitro, in vivo and more recently, in-patient data.

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“…The expanding drugs and inhibitors have been used that inhibition of hCAIX against various cancer and metabolic disorders as a molecule [17][18][19]. This knowledge prompted us to investigate the effects of different cytokines that crucial proteins for immunotherapy on expression of hCAIX critical proliferation mechanism of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

hCAIX Expression and Cell Cycle in Cytokine Stimulated Human Colon Cancer Cells

Sağkan

Köçkar

Şengül

et al. 2019

Preprint

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Background: At the aim of this study, we investigated the effects of different kind of cytokines and the combinations of which on human carbonic anhydrase IX ( hCAIX) expression in HT-29 cell selected as colon carcinoma model for different doses and time of exposure to determine role of cytokines for treatment of colon carcinoma cells. Results: To sum up, h CA9 expression in the levels of gene and protein increased in HT-29 cells when stimulated with 1000 U/mL TGF-β for 24 h. The stimulation of HT-29 cells with IL1 α alone and IL1α- TGF-β combination has not revealed any effect on hCA9 expression in both levels of gene and protein in contrast to, 1000 U/mL IL1α-TNFα and especially TGFβ-TNFα have reducing effect on h CA9 expression level in HT-29 cells for time ranges of 24 h, 48 h, 72 h. In addition to this data, it was observed that HT-29 cells at the phase of G0G1 are arrested in cell cycle when stimulated with either of 1000 U/mL IL1α-TNFα and TGFβ-TNFα. Moreover, it was observed that h CA9 expression level in HT-29 cells decreases at the phases of synthesis (S) and G2M. Discussion: We concluded that combination of TNFα-TGFβ has created antagonistic effect on hCA9 expression in HT-29 colon cancer cell model. On the other hand, combination of TNFα-IL1α caused sinergistic effect on h CA9 expression level in this cell model. When these results are demonstrated decrease in the cytokine exposed hCA9 expression is a finding to develop a novel approach for anticancer therapy. Conclusion: Our finding related to the change in the expression of hCA9 following cytokine stimulate to colon cancer cell line gives an idea about the effect of cytokine stimulation on the expression of this gene which will be a hot spot research in colon carcinogenesis. Methods: HT-29 colon cells were chosen as a colorectal adenocarcinoma model. hCA9 gene expression in the level of mRNA was measured in cytokines stimulated HT-29 cells by Quantitative Real-time PCR. Meanwhile, hCAIX expression in the level of protein and cell cycle aassay were detected by flow cytometry.

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Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines

Cited by 28 publications

References 46 publications

Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

hCAIX Expression and Cell Cycle in Cytokine Stimulated Human Colon Cancer Cells

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Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines

Cited by 28 publications

References 46 publications

Rh2(esp)2‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Rh2(esp)2‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

hCAIX Expression and Cell Cycle in Cytokine Stimulated Human Colon Cancer Cells

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Product

Resources

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Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines

Rh₂(esp)₂‐Catalyzed Coupling of α‐Diazo‐γ‐butyrolactams with Aromatic Amines