Conformationally Constrained Analogs of N‐Substituted Piperazinylquinolones: Synthesis and Antibacterial Activity of N‐(2,3‐Dihydro‐4‐hydroxyimino‐4H‐1‐benzopyran‐3‐yl)‐piperazinylquinolones

Abstract

A series of novel quinolone agents bearing a particular bulky and conformationally constrained bicyclic substituent (2,3-dihydro-4-hydroxyimino-4H-1-benzopyran-3-yl- moiety) on the piperazine ring of 7-piperazinyl quinolones (norfloxacin, enoxacin, ciprofloxacin, and levofloxacin) were synthesized and evaluated against a panel of Gram-positive and Gram-negative bacteria. Among these derivatives, ciprofloxacin counterpart 9c, highly inhibited the tested Gram-positive bacteria, superior to that of the reference drugs, and displayed antibacterial activity at non-cytotoxic concentrations.

In-Vitro Antibacterial / Antifungal Screening of 2-Chloroquinoline Scaffold Derivatives

“…The chloromethyl intermediate (17 and 18) were also showed weak activity which was observed at (MIC 200 µg/ml) against the test bacterial strains. While their corresponding secondary amines of sulphanilamide (19,20) and p-aminophenol (21,22) was comparatively more active in inhibiting the growth of the bacteria (MIC 12.5 to 25 µg/ml). Among the 2-mercaptobenzimidazole derivatives (23)(24)(25)(26), the nitro derivatives were more active against the all the bacterial strains and there MIC was observed in the range of 25-50 µg/ml.…”

“…The 2-chloro-3-formylquinoline and 2-chloro-3-formyl-6-methylquinoline (1, 2) were further reduced to alcohol (11,12) using solid NaBH 4 in methanol and subsequent reaction of 11 or 12 with benzoyl or p-methyl benzoyl chloride in pyridine affords various benzoate derivatives (13)(14)(15)(16). The chlorination of compounds (11,12) with SOCl 2 in dry benzene afforded intermediates 3-(chloromethyl)-2-chloroquinoline (17,18) and their successive nucleophilic substitution reaction with sulphanilamide or p-aminophenol in absolute ethanol in the presence of organic base triethylamine (TEA) gave 2-chloroquinolinyl amines (19)(20)(21)(22). While various 1 H-benzimidazol-2-ylsulfanyl)methyl (23)(24)(25)(26) derivatives were prepared by reacting intermediate (17,18) with 2-mercaptobenzimidazole or 2-mercapto-6-nitrobenzimidazole in ethanol in presence of base NaOH.…”

“…In IR spectra the characteristics C=O and C-O band for compounds (13)(14)(15)(16) were observed at 1724 -1730 and 1117-1123 cm -1 respectively. The synthesis of secondary amines (19)(20)(21)(22) of sulphanilamide/ p-aminophenol was identified by locating -CH 2 NH-function in spectral data. The 1 H-NMR signal due methylene of -CH 2 NH-was observed at δ value 4.59-4.62 ppm, while the NH proton was resonated at 4.30-4.38 ppm as singlet or broad singlet.…”

“…The antifungal activity of chloromethyl derivatives of 2-chloroquinoline (17 and 18) was found in the range of 50 to 100 µg/ml. The quinolinyl amine derivatives of sulphanilamide and p-amniophenol (19)(20)(21)(22) showed antifungal activity in the range of 25-100 µg/ml. The benzimidazole derivatives (23)(24)(25)(26) showed moderate antifungal activity against the test strain C. albicans, A. niger and A. flavus was and there MIC observed at 25 to 50 µg/ml.…”

Synthesis of Novel 4H-Chromenes Containing a Pyrimidine-2-Thione Function in the Presence of Fe3O4 Magnetic Nanoparticles and Study of Their Antioxidant Activity

“…Water is an obviously benign and inexpensive solvent to reduce pollution, cost, and tedious work-ups in synthetic methodologies. Bearing in mind the usefulness and efficiency of Fe 3 O 4 NPs in organic reactions 22 and in connection with our previous works on evaluation of biological active compounds, 23,24 we decided to explore an application of Fe 3 O 4 NPs for the preparation of 2-amino-4-aryl-4H-chromene-3-carbonitrile derivatives 5 with using multicomponent reaction 25 of 1, 2, and 4 (Scheme 1). Also, a novel series of chromenopyrimidinethione derivatives 8 were synthesized in order to develop novel antioxidant agents with low cytotoxicity activity.…”