Synthesis and Antibacterial Activity of Some Substituted 3-(Aryl)- and 3-(Heteroaryl)indoles

Summary. A synthesis of 3-(4-methoxycarbonyl-2,6-dinitrophenyl)indole, its 2,6-diamino analog, and 3-(2-amino-4-trifluoromethyl-6-nitrophenyl)indole is described. 4-(Trifluoromethyl)phenyl derivatives exhibit higher antibacterial potency than the former 4-(methoxycarbonyl)phenyl homologs, while 3-(4-trifluoromethyl-2-nitrophenyl)indole was the most active agent in the series, with MIC ≈ 7 μg/cm³ against E. coli and S. aureus.     

Synthesis and Antiproliferative and Antilipolytic Activities of a Series of 1,3- and 1,4-Bis[5-(R-sulfanyl)-1,2,4-triazol-3-yl)benzenes

Russian Journal of Organic Chemistry - A series of 1,3 and 1,4-bis[5-(R-sulfanyl)-1,2,4-triazol-3-yl)benzene derivatives were synthesized by the reaction of isophthalic and terephthalic acid...     

Dual anti-inflammatory and antiglycation propensities of a potentially novel class of functionalized fluoroquinolones

Promoted by elevated blood glucose concentrations in diabetes, glycation involves the nonenzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. New synthetic approaches to 18 fluoroquinolones (FQs) have been developed on the basis of a promising antiglycation activity using 400μM methylglyoxal as the choice glucocytotoxicity concentration. Their anti-inflammatory and radical scavenging properties were elucidated in vitro. Intriguingly, FQs could exhibit an exceedingly more superior than or substantially comparable cytoprotection against methylglyoxal-induced carbonyl toxicity in RAW264.7 macrophages and antiglycation activity to aminoguanidine, as the reference compound. This kind of activity can suggestively be associated with the chelating properties possessed by the synthesized FQs as their DPPH radical scavenging activities proved to be significantly inferior to those of the reference compound, the ascorbic acid. The inhibitory bioactivities using the Griess assay were examined of the compounds against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Selectively, compounds R-2TCBA , R-4FACBA , R-3TCBA , and R-4CLACBA exerted an exceedingly remarkable and superior anti-inflammatory effects (P < .001 vs indomethacin IC₅₀ value of 101.07 ± 2.2 μM) while R-4TCBA and T-4BrACBA were moderately more efficacious than indomethacin. Compounds T-4CLACBA and R-4BrACBA displayed comparable activity with indomethacin. None of the tested compounds and indomethacin exerted any cytotoxicity against RAW 264.7 mouse macrophages. FQs possess potent duality of antiglycation–anti-inflammatory capacities and are devoid of undesirable side effects. FQs can, therefore, serve as scaffolds for the development and designing of new clinical deglycation and antiglycation therapeutic agents.     

A Simple Dried Blood Spot Assay for Therapeutic Drug Monitoring of Lamotrigine

Blood spot collection cards can be easily used to obtain specimens for analysis of drugs for the purpose of therapeutic drug monitoring. In this work, the development and validation of a simple technique for the determination of lamotrigine from dried blood spots is described. The method is based on liquid chromatography with ultraviolet detection. The intra- and inter-day precision (measured by CV%) was less than 11%. The accuracy (measured by relative error %) was less than 12%. The limits of detection and quantification were calculated to be 0.12 and 0.2 μg mL^?1 respectively. The small volume of blood required (10 μL), the short analysis time (less than 4 min), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring lamotrigine concentrations. Our preliminary experience with the developed method indicated that it can be implemented in routine clinical setting.     

Antihyperlipidemic properties of novel N-(benzoylphenyl)-5-substituted-1H-indole-2-carboxamides in Triton WR-1339-induced hyperlipidemic rats

In the search for new potential antihyperlipidemic agents, the present study focuses on the synthesis of novel N-(benzoylphenyl)-5-substituted-1H-indole-2-carboxamides (compounds 8-12, 15, 16, 18) and investigating their antihyperlipidemic activity using Triton WR-1339-induced hyperlipidemic rats as an experimental model. Hyperlipidemia was developed by intraperitoneal injection of Triton WR-1339 (250 mg/kg body weight). The tested animals were divided into normal control (NCG), hyperlipidemic (HG), compound 8, 9, 15, 16, 18- and bezafibrate treated groups. At a dose of 15 mg/kg body weight, compounds 9, 16, 18 and bezafibrate (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 h compared to the hyperlipidemic control group. However, only the group treated with compounds 9, 16 and 18 showed an obviously significant (p < 0.001) reduction in plasma total cholesterol levels after 12 h compared to the hyperlipidemic control group. Moreover, high density lipoprotein-cholesterol levels were significantly (p < 0.0001) increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for compounds 8 and 15 which revealed inactive. It is therefore reasonable to assume that compounds 9, 16 and 18 may have potential in the treatment of hyperlipidemia.     

Synthesis and anti-hyperlipidemic evaluation of N‑(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats

The lipid-lowering activity of a series of novel N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives has been studied in Triton WR-1339-induced hyperlipidemia in rats. The test animals were divided into four groups: control, hyperlipidemic, compound + 4% DMSO [C1: N-(2-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (1), C2: N-(3-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (2), C3: N-(4-benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide (3)]-treated and bezafibrate (BF)-treated. At a dose of 15 mg/Kg body weight, compounds 2, 3 and BF significantly reduced elevated plasma triglycerodes levels after 12 h. Moreover, high density lipoprotein-cholesterol levels were significantly increased in all treated groups after 12 h compared to the hyperlipidemic control group, except for C1 which was inactive. In sum, it may be stated that the results of the present study demonstrated new properties of some N-(benzoylphenyl)-5-fluoro-1H-indole-2-carboxamide derivatives as potent lipid lowering agents and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.     

A Simple Dried Blood Spot Assay for Therapeutic Drug Monitoring of Lamotrigine

Blood spot collection cards can be easily used to obtain specimens for analysis of drugs for the purpose of therapeutic drug monitoring. In this work, the development and validation of a simple technique for the determination of lamotrigine from dried blood spots is described. The method is based on liquid chromatography with ultraviolet detection. The intra- and inter-day precision (measured by CV%) was less than 11%. The accuracy (measured by relative error %) was less than 12%. The limits of detection and quantification were calculated to be 0.12 and 0.2 μg mL⁻¹ respectively. The small volume of blood required (10 μL), the short analysis time (less than 4 min), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring lamotrigine concentrations. Our preliminary experience with the developed method indicated that it can be implemented in routine clinical setting.

     

Synthesis and antibacterial properties of new 8-nitrofluoroquinolone derivatives

The objective of this research was the preparation of new 8-nitrofluoroquinolone models and investigation of their antibacterial properties. The work initially involved large scale preparation of the synthon 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3), followed by introduction of substituted primary amine appendages at the C-7 position to give derivatives 9a-g, in which the amino group is appended to substituted benzenes or aromatic heterocycles, is part of a primary alpha-amino acid or just a simple primary aliphatic amine. This nucleophilic aromatic substitution step was a very simple procedure since the 8-nitro group of the above synthon facilitated the addition of weak nucleophiles at C-7. All compounds prepared were fully identified and characterized using NMR, IR, EA and MS, and were consistent with expected structures. The prepared targets and the intermediates have shown interesting antibacterial activity against gram positive and/or gram negative strains. In particular, the p-toluidine, p-chloroaniline and aniline derivatives showed good activity against S. aureus with MIC range approximately 2-5 microg/mL. In conclusion, more lipophilic groups seem to enhance activity against gram positive strains.