Easy-To-Access Quinolone Derivatives Exhibiting Antibacterial and Anti-Parasitic Activities

Autor: Dustin Laming, Digby F. Warner, Ronnett Seldon, Richard M. Beteck, Audrey Jordaan, Setshaba D. Khanye, Heinrich C. Hoppe
Rok vydání: 2021
Předmět:
Acinetobacter baumannii
Staphylococcus aureus
medicine.drug_class
human African trypanosomiasis
Antibiotics
Plasmodium falciparum
Trypanosoma brucei brucei
Antiprotozoal Agents
malaria
Pharmaceutical Science
Microbial Sensitivity Tests
Trypanosoma brucei
Quinolones
Article
Analytical Chemistry
Microbiology
lcsh:QD241-441
Cell wall
Mycobacterium tuberculosis
03 medical and health sciences
lcsh:Organic chemistry
Parasitic Sensitivity Tests
Drug Discovery
parasitic diseases
ESKAPE pathogens
medicine
anti-Mtb
Physical and Theoretical Chemistry
030304 developmental biology
0303 health sciences
biology
Dose-Response Relationship
Drug
Molecular Structure
030306 microbiology
Chemistry
Organic Chemistry
biology.organism_classification
Quinolone
Anti-Bacterial Agents
Chemistry (miscellaneous)
Antiprotozoal
Molecular Medicine
Bacteria
Zdroj: Molecules
Molecules, Vol 26, Iss 1141, p 1141 (2021)
Volume 26
Issue 4
ISSN: 1420-3049
Popis: The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24–31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4–20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje