Synthesis and In-vitro Antibacterial Activity of <I>N</I>-Piperazinyl Quinolone Derivatives with a 2-Thienyl Group

Abstract

Novel N‐substituted piperazinyl quinolones have been synthesized by reaction of piperazinyl quinolones with α‐bromo‐2‐acetylthiophene or α‐bromo‐2‐acetylthiophene oximes and evaluated for in‐vitro antibacterial activity. Compounds with a [2‐oxo‐2‐(2‐thienyl)ethyl] group had antibacterial activity against Gram‐positive and Gram‐negative bacteria similar to that of reference drugs, ciprofloxacin, norfloxacin and enoxacin. The oximes were almost as potent as the corresponding ketones against staphylococci but less active against Gram‐negative bacteria. Replacement of the hydrogen of the oxime with a methyl group resulted in greater antibacterial activity against both Gram‐positive and Gram‐negative bacteria, with minimum inhibitory concentrations (MIC) ranging from 0.0075 to 0.5 μg mL−1; this potency was greater than that of the reference compounds. The antibacterial activity of the O‐benzyloxime derivatives was lower. Ciprofloxacin derivatives were usually more active than norfloxacin or enoxacin derivatives.

Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies

“…The development of novel anticancer agents remains an important and a challenge goal in medicinal chemistry and therefore, developing new effective anticancer drugs is an important strategy in cancer treatment 3,4 . The antibacterial fluoroquinolones have been found to be one of the fastest growing groups of drugs in recent years [5][6][7][8] . Quinolones are known for their antibacterial and antitumor activities through alteration of the normal functions of bacterial gyrase, and are found to be a topoisomerase II inhibitor in humans [9][10][11][12][13][14][15][16][17][18] .…”

Synthesis and Antibacterial Activity of New N-[2-(Thiophen-3-yl)ethyl] Piperazinyl Quinolones

“…Similarly, the O-methyloxime ethers 8b and O-benzyloxime ethers 8c were synthesized by reaction of compound 7 with methoxyamine hydrochloride and O-benzylhydroxylamine hydrochloride, respectively. [10][11][12] Reaction of 7-piperazinylquinolones (1, 2 or 3) with 3-(bromoacetyl)thiophene 7 or a-bromooxime derivatives 8a-c in DMF, in the presence of NaHCO 3 at room temperature afforded corresponding ketones 5a-c and oxime derivatives 5d-l, respectively. [10][11][12] Accordingly, enoxacin 3 and ciprofloxacin 2 reacted with abromooxime 8a to give exclusively (E)-5d and (E)-5f.…”

“…[10][11][12] Reaction of 7-piperazinylquinolones (1, 2 or 3) with 3-(bromoacetyl)thiophene 7 or a-bromooxime derivatives 8a-c in DMF, in the presence of NaHCO 3 at room temperature afforded corresponding ketones 5a-c and oxime derivatives 5d-l, respectively. [10][11][12] Accordingly, enoxacin 3 and ciprofloxacin 2 reacted with abromooxime 8a to give exclusively (E)-5d and (E)-5f. However, in the reaction of norfloxacin 1 with a-bromooxime 8a, (E)-and (Z)-isomers of 5e were isolated in approximately a 65/35 ratio based upon comparison of the NMR integration of corresponding peaks from an aliquot of the principal product mixture.…”

“…The 2-bromo-1-(thiophen-3-yl)ethanone 7 and 2-bromo-1-(thiophen-3-yl)ethanone oxime derivatives 8 were prepared according to the literature methods. [10][11][12] Melting points were determined on a…”

“…1) solely by the linkage of various 2-(thiophen-2-yl)ethyl groups to the piperazinyl residue at C-7 of the parent drug and explored their antibacterial activities. [10][11][12] By considering the considerable activity of N- [2-(thiophen-2-yl)ethyl] piperazinyl quinolone derivatives 4 against Gram-negative and Grampositive bacteria, a new series of N- [2-(thiophen-3-yl)ethyl] derivatives of piperazinyl quinolone (5, Fig. 1) were also synthesized and evaluated for antibacterial activity as positional isomers of 4.…”