The history and rationale of using carbonic anhydrase inhibitors in the treatment of peptic ulcers. In memoriam Ioan Puşcaş (1932–2015)

Buzás, György Miklós; Supuran, Claudiu T.

doi:10.3109/14756366.2015.1051042

Cited by 71 publications

(35 citation statements)

References 54 publications

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“…In the 1970s, CAI was first used for the treatment of peptic ulcers by Ioan Puşcaş and colleagues [79]. The lack of unwanted side effects ultimately resulted in CAI being used for therapies against other medical conditions, and it eventually led to the discovery of CAI being used as an anti-cancer compound [79].…”

Section: Pathways Involved In Tumour Growthmentioning

confidence: 99%

Combination therapy in combating cancer

et al. 2017

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Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.

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Section: Pathways Involved In Tumour Growthmentioning

confidence: 99%

Combination therapy in combating cancer

et al. 2017

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“…Unexpectedly, the last identified i-CA, which is encoded in the genome of the marine diatom Thalassiosira pseudonana, prefers Mn 2þ to Zn 2þ as a cofactor 24 . In the CA active site, the metal is coordinated by three amino acid residues and, the fourth ligand is a water molecule/hydroxide ion acting as the nucleophile in the catalytic enzyme cycle 3,7,26,27,38,39 . The metal coordination is rather variegated among the CA-classes since in the a-, c-, dand, probably, h-classes the ion cofactor is coordinated by three His residues; by one His, and two Cys residues in band f-CAs; by two His and one Gln residues in the g-class 40 .…”

Section: Introductionmentioning

confidence: 99%

Bacterial ι-carbonic anhydrase: a new active class of carbonic anhydrase identified in the genome of the Gram-negative bacterium Burkholderia territorii

Prete

Nocentini

Capasso

2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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The carbonic anhydrases (CAs, EC 4.2.1.1) catalyse a simple but physiologically crucial reversible reaction, the carbon dioxide hydration with the production of bicarbonate and protons. In the last years, and especially, to the rapid emergence of the bacterial antibiotic resistance that is occurring worldwide, the understanding of the function of bacterial CAs has increased significantly. Recently, a new CA-class (i-CA) was discovered in the marine diatom T. pseudonana. It has been reported that bacterial genomes may contain genes with relevant homology to the diatom i-class CA. Still, the catalytic activity of the enzyme encoded by the gene was not investigated. Thus, herein, for the first time, we cloned, expressed, and purified the recombinant bacterial i-CA (acronym BteCAi) identified in the genome of Burkholderia territorii. The recombinant BteCAi resulted in a good catalyst for the hydration of CO 2 to bicarbonate and protons, with a k cat of 3.0 Â 10 5 s À1 and k cat /K M of 3.9 Â 10 7 M À1 s À1 , and is also sensitive to inhibition by the sulphonamide acetazolamide. Furthermore, with the aid of the protonography, it has been demonstrated that BteCAi can be present as a dimer. This result is corroborated by the construction of a molecular model of BteCAi, which showed that the enzyme is formed by two equivalent monomers having a structure similar to a butterfly.

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“…The last CA class was discovered recently analyzing the amino acid sequences of CAs from Plasmodia 5,[7][8][9][10][11] . The a-, b-, d-and Z-CAs use Zn(II) ions at the active site, the g-CAs are probably Fe(II) enzymes (but they are active also with bound Zn(II) or Co(II) ions), whereas the z-class are cambialistic enzymes, active both with Cd(II) or Zn(II) bound within the active site 3,4,[12][13][14][15][16][17][18][19] . The metal ion from the enzyme active site is coordinated by three histidine (His) residues (in the a-, g-d-class enzymes) or by one His, and two cysteine (Cys) residues (in the band z-CAs), with the fourth ligand being a water molecule/ hydroxide ion acting as nucleophile in the catalytic cycle of the enzyme.…”

Section: Carbonic Anhydrase Familymentioning

confidence: 99%

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

Supuran

Capasso

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Among protein families, carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes characterized by a common reaction mechanism in all life domains: the carbon dioxide hydration to bicarbonate and protons (CO 2 +H 2 O () HCO 3 À +H + ). Six genetically distinct CA families are known to date, the a-, b-, g-, d-, z-and Z-CAs. The last CA class was recently discovered analyzing the amino acid sequences of CAs from Plasmodia. Bacteria encode for enzymes belonging to the a-, b-, and g-CA classes and recently, phylogenetic analysis revealed an interesting relationship regarding the evolution of bacterial CA classes. This result evidenced that the three bacterial CA classes, in spite of the high level of the structural similarity, are evolutionarily distinct, but we noted that the primary structure of some b-CAs identified in the genome of Gram-negative bacteria present a pre-sequence of 18 or more amino acid residues at the N-terminal part. These observations and subsequent phylogenetic data presented here prompted us to propose that the b-CAs found in Gram-negative bacteria with a periplasmic space and characterized by the presence of a signal peptide might have a periplasmic localization and a role similar to that described previously for the a-CAs.

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The history and rationale of using carbonic anhydrase inhibitors in the treatment of peptic ulcers. In memoriam Ioan Puşcaş (1932–2015)

Abstract: Carbonic anhydrase (CA, EC 4.2

Cited by 71 publications

References 54 publications

Combination therapy in combating cancer

Combination therapy in combating cancer

Bacterial ι-carbonic anhydrase: a new active class of carbonic anhydrase identified in the genome of the Gram-negative bacterium Burkholderia territorii

New light on bacterial carbonic anhydrases phylogeny based on the analysis of signal peptide sequences

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