Abstract:
This work aimed at improving efficacy and reducing toxicity of non-steroidal anti-
inflammatory (NSAIDs) and anti-bacterial drugs by designing and synthesizing mutual
prodrugs with dual activities. The NSAIDs were ibuprofen, flurbiprofen and aspirin, which
contained a carboxylic group as part of their structure. The antibacterial included ampicillin,
metronidazole, isoniazid, sulfamethoxazole, sulfamerazine, sulfamethazine, sulfanilamide, 7-
ADCA and 7-AVCA, which contained an amino group as part of their structure. In the
prodrugs of these compounds the two drugs were covalently linked together forming an
amide linkage. In addition to these a prodrug from benzydamine, containing amino group,
and cefazoline, containing carboxylic group was synthesized, in which the two drugs formed
a quaternary ammonium salt. All the synthesized compounds were characterized by use of
diverse analytical techniques including elemental analysis, FT-IR, electronic spectra, 1H and
13
C NMR, ESI-MS and single crystal XRD techniques.
The new compounds were subjected to anti-bacterial, anti-inflammatory, enzyme inhibition
and toxicity tests in order to evaluate them as more effective and safe drugs with dual
activities. Some of the activity related properties, which could not be determined
experimentally, were determined through computational analysis. The results showed that
aspirin, flurbiprofen and ibuprofen prodrugs perform better (having moderate to significant
difference) than the parent drugs in anti-bacterial and anti-inflammatory tests. The
computational analysis also suggests that the prodrugs possess better druglike properties and
bioavailability with slight variations. Thus this study clearly indicates that mutual prodrug is
an advantageous option where a concomitant treatment is required.
