Inhibition studies of quinazoline-sulfonamide derivatives against the γ-CA (PgiCA) from the pathogenic bacterium,<i>Porphyromonas gingivalis</i>

Alafeefy, Ahmed M.; Ceruso, Mariangela; Al-Tamimi, Abdul-Malek S.; Prete, Sonia Del; Supuran, Claudiu T.; Capasso, Clemente

doi:10.3109/14756366.2014.957202

Cited by 48 publications

(18 citation statements)

References 30 publications

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“…Bacterial carbonic anhydrase evolution Bacteria encode for enzymes belonging to the a-, b-, and g-CA classes and recently, we have conducted a thorough phylogenetic analysis to better understand the evolutionary relationship among the bacterial CA classes (Figure 1) [25][26][27][28][29][30][31][32][33][34][35][36][37] . Table 1 reports the list of the bacterial species and the accession numbers of the amino acid sequences of CAs examined for constructing the phylogenetic tree of Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…On the contrary, b-or g-classes have a cytoplasmic localization and are responsible of CO 2 supply for carboxylase enzymes, pH homeostasis and other intracellular functions 3 . The most interesting aspect appearing from the phylogenetic analysis reported in Figure 1 was the amino acid sequence of the b-CA identified in the genome of Porphyromonas gingivalis (PgiCAbeta), a Gram-negative oral pathogenic bacterium 29,30,33,[48][49][50][51][52][53] . This enzyme can be considered as a ''turning sequence'', which led to the bacterial a-CAs, which are present only in Gram-negative bacteria.…”

Section: New Insight In the B-cas Evolutionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: New Insight In the B-cas Evolutionmentioning

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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“…47 The kinetic parameters for BpsCAc were: k cat of 5. hydrase activity when compared with the human isoform hCA I, which is similar to the bacterial c-CAs from various pathogenic bacteria (Porphyromonas gingivalis, an oral cavity pathogenic bacterium; Vibrio cholerae, etiological agent of cholera; Table 1). 10,13,30,34,42,[48][49][50] Furthermore, the BpsCAc activity was effectively inhibited (K I of 149 nM) by the clinically used sulfonamide inhibitor acetazolamide.…”

Section: àmentioning

confidence: 96%

Sulfonamide inhibition profile of the γ-carbonic anhydrase identified in the genome of the pathogenic bacterium Burkholderia pseudomallei the etiological agent responsible of melioidosis

Prete

Vullo

Fonzo

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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“…Moreover, novel quinazoline derivatives endowed with a sulfonamide functionality at position-2 were tested for their ability to inhibit PgiCA [90]. Six such compounds were highly effective, nanomolar inhibitors of the pathogenic enzyme.…”

Section: Pgicamentioning

confidence: 99%

“…Among the bacteria regularly isolated from periodontal pockets, those producing such pathological states are generally gramnegative rods and include mainly Porphyromonas gingivalis, and other such as Prevotella intermedia, Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Capnocytophaga sputigena, and Wolinella recta [84,85]. As many other bacteria, the genome of P. gingivalis encodes for both a β-and γ-CA named with the acronyms PgiCAβ and PgiCA, respectively [8,22,28,[86][87][88][89][90][91].…”

Section: Two Pathogenic Bacteria From the Oral Cavity P Gingivalis mentioning

confidence: 99%

Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

Capasso

Supuran

2017

CTMC

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Background: Clinically used antibiotics act through one of these four mechanisms: cell wall biosynthesis inhibition, inhibition of protein biosynthesis, interference with DNA and RNA synthesis and the folate pathway. Objective:The metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) widespread in microorganisms and present as three genetically distinct families may be considered for the design of antiinfective agents with a different mechanism of action compared to the clinically used antibiotics. CAs are crucial for the life cycle of the pathogen, interfering with pH regulation and biosynthetic processes in which CO 2 or bicarbonate are substrates. CA inhibition was shown to lead to debilitation or growth defects of several pathogenic bacteria. Method:CAs catalyzes the interconversion between carbon dioxide to bicarbonate, leading to the formation of protons, and thus affecting pH homeostasis. Several classes of CA inhibitors (CAIs) are known to date, among which the metal complexing anions, the unsubstituted sulfonamides, the dithiocarbamates, etc., which bind to the Zn(II) ion of the enzyme either by substituting the non-protein zinc ligand or add to the metal coordination sphere.Results: Effective inhibitors for many bacterial CAs belonging to the α-, β-, and γ-CA classes were detected, some of which inhibited bacterial growth in vivo. Few of the inhibitors investigated so far were also selective for the bacterial over the human CA isoforms, which may pose problems for their wide clinical applications. Conclusion:Structure-based drug design campaigns might lead to the achievement of the desired selectivity/potency for preferentially inhibiting bacterial but not the host CAs.

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Inhibition studies of quinazoline-sulfonamide derivatives against the γ-CA (PgiCA) from the pathogenic bacterium,Porphyromonas gingivalis

Cited by 48 publications

References 30 publications

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

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

Sulfonamide inhibition profile of the γ-carbonic anhydrase identified in the genome of the pathogenic bacterium Burkholderia pseudomallei the etiological agent responsible of melioidosis

Inhibition of Bacterial Carbonic Anhydrases as a Novel Approach to Escape Drug Resistance

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