Structure and inhibition studies of a type II beta-carbonic anhydrase psCA3 from Pseudomonas aeruginosa

AbstractThe Aerva plants are exceptionally rich in phytochemicals and possess therapeutics potential. Phytochemical screening shows that Aerva persica (Burm.f.) Merr. contains highest contents i.e., total phenolics, flavonoids, flavonols, tannins, alkaloids, carbohydrates, anthraquinones and glycosides. In-vitro antibacterial and enzymatic (carbonic anhydrase) inhibition studies on methanol extracts of A. persica indicated the presence of biological active constituents within chloroform soluble portions. Investigation in the pure constituents on the chloroform portions of A. persica accomplished by column chromatography, NMR and MS analysis. The bioguided isolation yields four chemical constituents of coumaronochromone family, namely aervin (1-4). These pure chemical entities (1-4) showed significant antibacterial activity in the range of 60.05–79.21 µg/ml against various bacterial strains using ampicillin and ciprofloxacin as standard drugs. The compounds 1-4 showed promising carbonic anhydrase inhibition with IC50 values of 19.01, 18.24, 18.65 and 12.92 µM, respectively, using standard inhibitor acetazolamide. First-principles calculations revealed comprehensive intramolecular charge transfer in the studied compounds 1-4. The spatial distribution of highest occupied and lowest unoccupied molecular orbitals, ionization potential, molecular electrostatic potential and Hirshfeld analysis revealed that these coumaronochromone compounds would be proficient biological active compounds. These pure constituents may be used as a new pharmacophore to treat leaukomia, epilepsy, glaucoma and cystic fibrosis.

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Anion inhibition studies of the Zn(II)-bound ι-carbonic anhydrase from the Gram-negative bacterium Burkholderia territorii

Journal of Enzyme Inhibition and Medicinal Chemistry ◽

10.1080/14756366.2020.1867122 ◽

2021 ◽

Vol 36 (1) ◽

pp. 372-376

Author(s):

Andrea Petreni ◽

Viviana De Luca ◽

Andrea Scaloni ◽

Alessio Nocentini ◽

Clemente Capasso ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Negative Bacterium ◽

Gram Negative ◽

Inhibition Studies

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Synthesis and Human Carbonic Anhydrase I, II, IX, and XII Inhibition Studies of Sulphonamides Incorporating Mono-, Bi- and Tricyclic Imide Moieties

Pharmaceuticals ◽

10.3390/ph14070693 ◽

2021 ◽

Vol 14 (7) ◽

pp. 693

Author(s):

Kalyan K. Sethi ◽

KM Abha Mishra ◽

Saurabh M. Verma ◽

Daniela Vullo ◽

Fabrizio Carta ◽

...

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

Docking Studies ◽

Carbonic Anhydrases ◽

Molecular Docking Studies ◽

Structure Activity Relationships ◽

Structure Activity ◽

Carbonic Anhydrase I ◽

Human Carbonic Anhydrase ◽

Inhibition Studies

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure–activity relationships (SAR) are rationalised with the help of molecular docking studies.

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In vitro synthesis of poly(3-hydroxydecanoate): purification and enzymatic characterization of type II polyhydroxyalkanoate synthases PhaC1 and PhaC2 from Pseudomonas aeruginosa

Applied Microbiology and Biotechnology ◽

10.1007/s002530000357 ◽

2000 ◽

Vol 54 (1) ◽

pp. 37-43 ◽

Cited By ~ 54

Author(s):

Q. Qi ◽

A. Steinbüchel ◽

B. H. A. Rehm

Keyword(s):

Pseudomonas Aeruginosa ◽

Type Ii ◽

Enzymatic Characterization ◽

In Vitro Synthesis

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Identification of type II and type III pyoverdine receptors from Pseudomonas aeruginosa

Microbiology ◽

10.1099/mic.0.26136-0 ◽

2003 ◽

Vol 149 (4) ◽

pp. 821-831 ◽

Cited By ~ 66

Author(s):

Magaly de Chial ◽

Bart Ghysels ◽

Scott A. Beatson ◽

Valérie Geoffroy ◽

Jean Marie Meyer ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Type Ii ◽

Type Iii

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Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00148-07 ◽

2007 ◽

Vol 51 (11) ◽

pp. 4062-4070 ◽

Cited By ~ 105

Author(s):

B. Henrichfreise ◽

I. Wiegand ◽

W. Pfister ◽

B. Wiedemann

Keyword(s):

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

Acquired Resistance ◽

Resistance Mechanisms ◽

Type Ii ◽

Mechanisms Of Resistance ◽

Resistance Determinants ◽

Class 1 ◽

Mutator Strains ◽

Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

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