Twenty six α-substituted
N4-acetamide derivatives of
ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against
Pseudomonas aeruginosa,
Escherichia coli,
Staphylococcus aureus and
Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives,
CD-7 (Ar = 3-chlorophenyl),
CD-9 (Ar = 2-pyrimidyl) and
CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against
Staphylococcus aureus than CIPRO, while only compound
CD-10 exhibited better activity, 0.1 μM, against
Bacillus subtilis than CIPRO. In addition, compounds
CD-5 (Ar = 2-methoxyphenyl),
CD-6 (α-phenyl, Ar = 2-methoxyphenyl),
CD-7 (Ar = 3-Chlorophenyl),
CD-8 (α-phenyl, Ar = 3-chlorophenyl) and
CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against
Staphylococcus aureus, although
ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and
ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives,
ND-7 and
ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against
Bacillus subtilis, while compounds
ND-8 (α-phenyl, Ar = 3-chlorophenyl) and
ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain
. QSAR revealed that while polarity is the major contributing factor in the potency against
Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against
Bacillus subtilis, with a lesser and variable effect for lipophilicity.
Full article