Design, synthesis and antimicrobial evaluation of propylene-tethered ciprofloxacin-isatin hybrids.
Eur J Med Chem
; 156: 580-586, 2018 Aug 05.
Article
in En
| MEDLINE
| ID: mdl-30025351
ABSTRACT
Twelve novel propylene-tethered ciprofloxacin-isatin hybrids 3a-f and 4a-f were designed, synthesized and characterized by MS, HRMS, 1H NMR and 13C NMR. All hybrids were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and mycobacterial pathogens, cytotoxicity in VERO cell line as well as metabolic stability and in vivo pharmacokinetic (PK) properties. The preliminary results indicated that all mono-isatin-ciprofloxacin hybrids exhibited excellent antibacterial activities with MIC ranging from ≤0.03 to 0.5⯵g/mL against most of the tested strains. In particular, ciprofloxacin-isatin hybrid 3d was highly potent against all tested Gram-positive and Gram-negative strains including clinically important drug-resistant pathogens, which was comparable to or more potent than the parent ciprofloxacin and reference levofloxacin. Whereas, conjugate 3b (MIC 0.10 and 0.5⯵g/mL) was 4- and 8-fold more active than ciprofloxacin (MIC 0.78⯵g/mL) and rifampicin (MIC 0.39⯵g/mL) against MTB H37Rv, and 4->256 times more potent than the three references ciprofloxacin (MIC 2.0⯵g/mL), rifampicin (MIC 32⯵g/mL) and isoniazid (>128⯵g/mL) against MDR-TB. Both hybrid 3b and 3d with low cytotoxicity (CC50 64 and 256⯵g/mL) also showed acceptable metabolic stability and in vivo PK properties, could act as leads for further optimization.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacteria
/
Ciprofloxacin
/
Alkenes
/
Anti-Bacterial Agents
Limits:
Animals
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Female
/
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2018
Document type:
Article