Design, Synthesis and Molecular Docking of 1-Cyclopropyl-6- Fluoro-4-Oxo-7-{4-[2-(4-Substituted-Phenyl)-2-(Substituted)-Ethyl] -1-Piperazinyl}-1,4-Dihydroquinoline-3-Carboxylic Acid as an Antimicrobial Agents.

BACKGROUND: Quinolone scaffolds are widely used for the synthesis of a number of medicinal compounds with variety of biological activity. In view of the reported antimicrobial activity of various fluoroquinolones, the structure activity studies of various substituted quinolones, which proved the importance of the C-7 substituents to exhibit potent antimicrobial activities. OBJECTIVE: Based on the structural activity relationship at C-7 position it was rationalized to design and synthesize new quinolone derivatives with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold. METHODS: A novel series of 1-cyclopropyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted-phenyl)- 2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized by reacting 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4- dihydroquinoline-3-carboxylic acid with 2-bromo-4-(substituted) acetophenone in the presence of sodium bicarbonate to obtain 1-cyclopropyl-6-fluoro-7-{4-[2-(4- substitutedphenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acids 2a-2d. Compound 2a-2d underwent further reaction with different substituted hydrazide, hydroxylamine hydrochloride or methoxylamine in glacial acetic acid to give 3a-7d. In vitro antibacterial activity of the synthesized compounds 3a-7d was studied and the MIC value was determined by the broth dilution method. RESULT: Among all the synthesized compounds 3a-7d some compounds showed antimicrobial activity in comparison to the reference standard ciprofloxacin. CONCLUSION: The compound 6d showed the reasonable good antibacterial activity among all the tested compounds. To understand antibacterial data on structural basis and the interaction of binding sites with bacterial protein receptor, the docking studies were carried out using topoisomerase II DNA gyrase enzymes (PDB ID. 2XCT) by shrodinger's maestro program.

Design, synthesis, molecular docking, and antibacterial evaluation of some novel flouroquinolone derivatives as potent antibacterial agent.

OBJECTIVE: Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. METHODS: A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl)-2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT) by Schrodinger's Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. RESULTS: Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. CONCLUSION: This investigation identified the potent antibacterial agents against certain infections.

Stability-indicating reversed-phase liquid chromatographic method for simultaneous determination of atorvastatin and ezetimibe from their combination drug products.

A simple, precise, and rapid stability-indicating reversed-phase column liquid chromatographic (RP-LC) method has been developed and subsequently validated for simultaneous estimation of atorvastatin (ATV) and ezetimibe (EZE) from their combination drug product. The proposed RP-LC method utilizes a LiChrospher 100 C18, 5 microm, 250 x 4.0 mm id column at ambient temperature; the optimum mobile phase consists of acetonitrile-water-methanol (45 + 40 + 15, v/v/v) with apparent pH adjusted to 4.0 +/- 0.1; mobile phase flow rate of 1.0 mL/min; and UV detection at 250 nm. ATV, EZE, and their combination drug product were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. There were no other coeluting, interfering peaks from excipients, impurities, or degradation products due to variable stress conditions, and the method is specific for the estimation of ATV and EZE in the presence of degradation products. The response was linear over the concentration range of 1-80 microg/mL for ATV and EZE. The mean recoveries were 99.27 and 98.5% for ATV and EZE, respectively. The intermediate precision data were obtained under different experimental conditions, and the calculated value of the coefficient of variation was found to be less than the critical value. The proposed method can be useful in the quality control of bulk manufacturing and pharmaceutical dosage forms.