Research: SYNTHESIS OF NEW LEVOFLOXACIN DERIVATIVES AND THEIR BIOLOGICAL ACTIVITY

Heterocyclic moieties like 2-aminobenzotriazole and 5-amino-2-mercapto-1,3,4-thiadiazole have been shown to have antibacterial, antifungal, anti-inflammatory and antitumer activities etc. Meanwhile quinolones as essential antibacterial agents are of important clinical and scientific interest in their discovery based on nalidixic acid. This attract our attention to synthesize novel compounds as important quinolone derivatives of levofloxacin linked once to 2-aminobenzotriazole and next to 5-amino-2-mercapto-1,3,4-thiadiazole with the aim of the possibility of ultering the side chain (carboxlic acid moiety) of levofloxacin to minimize the side effects of levofloxacin on gastrointestinal tract including gastric irritation and to alleviate it's side effects on joints at the same time enhancing or maintaining its antibacterial and other biological activities. The method includes the synthesis of two analogues of levofloxacin by introducing first: 2-aminobenzotiazole linked to the carboxyl moiety of levofloxacin and second: 5-amino-2-mercapto-1,3,4,thiadiazole linked at the same site of levofloxacin. For this purpose, 2-aminobenzotriazole was synthesized from benzene1,2-diamine followed by amination. Whereas 5-amino-2-mercapto-1,3,4,thiadiazole was synthesized through rearrangement of thiosemicarbazide with carbon disulphide by hot fusion. Then this step will be followed by condensation of levofloxacin via coupling reaction between the carboxylic group moiety of levofloxacin first with the amino group of 2-aminobenzotiazole and second with the amino group of 5-amino-2-mercapto-1,3,4,thiadiazole through the conventional coupling reaction using N,N-Dicyclohexylcarcodiimide (DCC) and 1-Hydroxybenzotriazole (HOBT) to obtain potent, save and higher yield products. Screening of the antimicrobial activity including antibacterial and antifungal of the two analogues was carried on using combinational agar dilution method and the inhibition zone was measured by comparism to Ofloxacin as reference drug for antibacterial activity and ketoconazol for antifungal activity of the tested compounds. The structural formula of the two analogues were consistent with the proposed structure as they were proved and characterized by different techniques i.e. melting point (m.p.), Thin layer chromatography(TLC), FTIR, Elemental microanalysis (CHNOS and F). Screening of the antimicrobial activity revealed that both analogues have significant activity both as antibacterial and antifungal. In conclusion, this work has successfully introduced new substituted amine appendages at C3 of fluo