N-substituted piperazinyl sarafloxacin derivatives: synthesis and in vitro antibacterial evaluation.

BACKGROUND: Fluoroquinolones (FQs) are compounds of major interest with broad antimicrobial activities against community and hospital-acquired infections such as respiratory tract infections (nosocomial pneumonia, chronic bronchitis and tuberculosis), skin and soft tissue infections, bone and joint infections, intra-abdominal infections and sexually transmitted diseases. This broad range of activities along with favorable pharmacokinetic and low toxicity introduced this class of compounds as important antimicrobial chemotherapy agents. The rapid increase in prevalence of FQs resistant microbes in environment motivated medicinal chemists to discover new quinolone-based compounds with potent activities against Gram-positive bacteria. METHODS: The designed compounds were prepared through the two-component reaction between aromatic α-haloketones or α-halooximes and sarafloxacin in the presence of NaHCO3 in DMF, affording the corresponding N-[2-(aryl-3-yl) ethyl] piperazinyl quinolone derivatives in good yields. All synthesized compounds were evaluated for antibacterial activities against Gram-positive [Staphylococcus aureus ATCC 6538p, Micrococcus luteus, ATCC 1110, Staphylococcus epidermidis ATCC 12228 and Bacillus subtilis ATCC 6633] and Gram-negative [Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 10031 Pseudomonas aeruginosa ATCC 9027 and Serratia marcescens PTCC 1111] bacteria. RESULTS: The antibacterial activities of 24 new compounds were reported as MIC values in comparison to sarafloxacin. The most active compound, 4 g, exhibited similar inhibitory activity against Gram-positive bacteria including S. aureus, S. epidermidis and B. subtilis compared to positive control. Furthermore, benzyloxime incorporated derivatives (4 s-4x) showed poor activity against all tested strains, except 4x. CONCLUSION: The obtained results indicated that the synthesized compounds containing substituted piperazine moiety at the C-7 position displayed same or weak inhibitory activities compared to sarafloxacin. Graphical abstract ᅟ.

Design, synthesis, molecular modeling and anticholinesterase activity of benzylidene-benzofuran-3-ones containing cyclic amine side chain.

AIM: A series of 2-benzylidene-benzofuran-3-ones were designed from the structures of Ebselen analogs and aurone derivatives and synthesized in good yields. MATERIALS & METHODS: The target compounds were prepared by the condensation reaction between appropriate benzofuranones with amino alkoxy aldehydes and evaluated as cholinesterase inhibitors by Ellman's method. RESULTS: The in vitro anti-acetylcholinesterase (AChE)/butyrylcholinesterase activities of the synthesized compounds revealed that 7e (IC50 = 0.045 µM) is the most active compound against AChE. Furthermore, the docking study confirmed the results obtained through in vitro experiments and predicted the possible binding conformation. CONCLUSION: The anticholinesterase activities of benzylidene-benzofurane-3-ones as aurone analogs revealed that the compounds bearing piperidinylethoxy residue showed better activities against AChE, introducing these compounds for further drug discovery developments. [Formula: see text].

Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents.

A series of 2-aryl-3-nitro-2H-chromenes 4a-u were designed as hybrid analogs of flavanone, ß-nitrostyrene and nitrovinylstilbene scaffolds. They were synthesized from the reaction of appropriate ß-nitrostyrenes and salicylaldehydes in good yields. In vitro cytotoxic activities of compounds 4a-u were tested against breast cancer cell lines including MCF-7, T-47D and MDA-MB-231. Most compounds exhibited good cytotoxic activity against selected cell lines, being more potent than standard drug etoposide. Representatively, 8-methoxy-3-nitro-2-(4-chlorophenyl)-2H-chromene (4l) with IC50 = 0.2 µM against MCF-7 cells, was 36-times more potent than etoposide. Apoptosis as a mechanism of cell death for selected compounds 4h and 4l was confirmed morphologically by acridine orange/ethidium bromide double staining and TUNEL analysis, as well as caspase-3 activation assay.