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Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...
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Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
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Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
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Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
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Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
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Non-sulfonamide bacterial CA inhibitors.

Fabrizio Carta1

  • 1NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Sesto Fiorentino, Florence, Italy.

The Enzymes
|September 2, 2024
PubMed
Summary

Non-sulfonamide compounds offer a promising alternative for inhibiting bacterial carbonic anhydrases (bCAs). These diverse chemical classes, including natural products, show potential for developing new antibacterial strategies.

Keywords:
Bacterial carbonic anhydrasesCoumarinsDithiocarbamatesIonsMonothiocarbamatesN-Hydroxy ureasN-Methyl thiosemicarbazonesPhenolsThiocoumarinsXanthates

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Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Enzymology

Background:

  • Bacterial carbonic anhydrases (bCAs) are essential enzymes and potential drug targets.
  • Traditional inhibitors often face limitations, necessitating alternative approaches.
  • Non-sulfonamide compounds represent a diverse and largely unexplored chemical space for bCA inhibition.

Purpose of the Study:

  • To explore novel non-sulfonamide chemical moieties as inhibitors of bacterial carbonic anhydrases (bCAs).
  • To identify and characterize diverse classes of compounds with potential bCA inhibitory activity.
  • To provide a foundation for the development of new therapeutic agents targeting bCAs.

Main Methods:

  • In vitro profiling of various non-sulfonamide compound classes against bacterial carbonic anhydrases.
  • Enzyme inhibition assays to determine the efficacy of identified compounds.
  • Chemical class diversity analysis of identified inhibitors.

Main Results:

  • Several distinct classes of non-sulfonamide compounds demonstrated significant in vitro inhibition of bCAs.
  • The identified compounds represent a broad range of chemical structures, including natural products.
  • This study validates the potential of these novel moieties for further development.

Conclusions:

  • Non-sulfonamide compounds are a viable and diverse alternative to sulfonamides for targeting bacterial carbonic anhydrases.
  • The identified chemical classes warrant further investigation for their therapeutic potential against bacterial infections.
  • This research opens new avenues for the development of novel antibacterial agents by targeting bCAs.