The present study aims to facilitate the development of new agents with better properties specifically, we focus on modifying the basic structure of quinolones; by introducing new functionality at its C3 position. For this purpose, a series of new conjugation derivatives (IIa-Vb) were designed and synthesized by esterification of quinolones (ciprofloxacin, gatifloxacin, nalidixic acid and norfloxacin) with two types of antioxidants (a: menthol and b: umbelliferone) at their carboxylic group at the C3 position which was replaced by an ester group through a glycol linker. The synthesized compounds were checked and characterized for their purity and chemical structure by spectral techniques (NMR, ATR-FTIR) also they were examined for their Pharmacological activities. In vivo, the anti-inflammatory effect of (IIa-Vb) compounds was estimated using a rat paw edema model and showed good activity for the end compounds IIa and IId, and their anti-inflammatory and antimicrobial effects were subsequently evaluated virtually-molecularly analyzed ; all prepared compounds show-interesting activity compared to the DMSO control group (solvent and control). The new conjugation derivatives were further tested about their antimicrobial activity against both grams positive and gram-negative bacteria , using the well diffusion method; the results showed that all eight synthesized compounds exhibited significant (high) antibacterial activity against gram-negative bacteria (Escherichia coli) compared to the reference drug (ciprofloxacin): (IIa and IIb) in concentration 50 mg, (IIa , IIb and IIIb) in concentration 25 mg (IIa , IIb , IIIb and Va) in concentration 12.5 mg. Higher inhibition and significant activity against gram-positive bacteria (Staphylococcus aureus) were demonstrated with quinoline derivatives: (IIa) in concentrations 50-25 mg, (IIa and Va) in concentration 12.5 mg. The other tested compounds showed good activity against bacterial species, ranging from equal, moderate to acceptable activity. Also the synthesized compounds shown significant antifungal activity against (Candida albicans) when compared with Fluconazole drug :( IIa, IVb, Va and Vb) in concentration 50 mg, (IIa ,Va and Vb) in concentration 25 mg. ADMET analysis of quasi-active molecules was performed and demonstrated an acceptable drug-like profile and desirable pharmacokinetic properties.