An Alternative Method for the Selective Synthesis of Ortho-nitro Anilines Using Bismuth Nitrate Pentahydrate.

BACKGROUND: Nitroaromatic compounds are important scaffolds used for the syn-thesis of a variety of compounds, such as explosives, herbicides, dyes, perfumes and phar-maceuticals. Bismuth nitrate pentahydrate is a widely used reagent in organic synthesis; how-ever, its utility as a nitrating agent for anilines is underexplored. OBJECTIVE: The aim of this work is to propose and find the proper reaction conditions of an alternative nitrating agent constituted by a mixture of bismuth nitrate / acetic anhydride in DCM with a series of substituted anilines under mild reflux. METHODS: Several anilines having both activating and deactivating substituents in the ortho, meta and para positions were the substrate for the nitration reaction. Experimental conditions were performed in "one-pot" conditions before product purification. RESULTS: Bi(NO3)3•5H2O demonstrated to be effective and somehow regioselective when it came to the nitration of anilines in the ortho position. Although other products were also identified under these conditions, in most cases, the ortho derivative was the major or even the only product obtained with moderate to high yields in the range of 50% - 96%. CONCLUSION: Bi(NO3)3•5H2O is an efficient and safe nitrating agent since the use of concen-trated and corrosive acids like sulfuric and nitric is avoided; furthermore, bismuth nitrate is low-priced and no special care nor equipment is required.

Novel ciprofloxacin and norfloxacin-tetrazole hybrids as potential antibacterial and antiviral agents: Targeting S. aureus topoisomerase and SARS-CoV-2-MPro.

This study was designed to synthesize hybridizing molecules from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining suitable statistical parameters ( R 2 = 87.00 , Q L M O 2 = 71.67 , and Q E X T 2 = 73.49 ) to support our results. The binding interaction of our compounds with CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds.

A Panoramic Review of Benzimidazole Derivatives and their Potential Biological Activity.

The therapeutic potential of the benzimidazole nucleus has been recognized since 1944, and it is an important heterocycle system due to its presence in a wide range of bioactive compounds such as antiviral, anticancer, antibacterial, and so on, where optimization of substituents in this class of pharmacophore has resulted in many drugs. Its broad biological activity stems from physicochemical properties such as hydrogen bond donor-acceptor capability, π→π stacking interactions, coordination bonds with metals as ligands and hydrophobic interactions; properties that allow them to easily bind with a series of biomolecules, including enzymes and nucleic acids, causing a growing interest in these types of molecules. This review aims to present an overview to leading benzimidazole derivatives, as well as to show the importance of the nature and type of substituents at the N1, C2, and C5(6) positions when they are biologically evaluated, which can lead to obtaining potent drug candidate with a significant range of biological activities.

Synthesis of 1,4-Biphenyl-triazole Derivatives as Possible 17ß-HSD1 Inhibitors: An in Silico Study.

Triazoles occupy an important position in medicinal chemistry because of their various biological activities. The structural features of 1,2,3-triazoles enable them to act as a bioisostere of different functional groups such as amide, ester, carboxylic acid, and heterocycle, being capable of forming hydrogen bonds and π-π interactions or coordinate metal ions with biological targets. In this work, the synthesis of 1,2,3-triazole derivatives via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is reported. Overexpression of 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1) is often found in breast cancer cells. Molecular similarity and docking analysis were used to evaluate the potential inhibitory activity of 1,2,3-triazoles synthesized over 17ß-HSD1 for the treatment of mammary tumors. Our in silico analysis shows that compounds 4c, 4d, 4f, 4g, and 4j are good molecular scaffold candidates as 17ß-HSD1 inhibitors.

In vitro Antibacterial Activity of 7-Substituted-6-Fluoroquinolone and 7-Substituted-6,8-Difluoroquinolone Derivatives.

BACKGROUND: Fluoroquinolones are widely prescribed synthetic antimicrobial agents. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome; the irreversible DNA damage eventually causes the killing of bacteria. Thorough knowledge of the structure-activity relationship of quinolones is essential for the development of new drugs with improved activity against resistant strains. METHODS: The compounds were screened for their antibacterial activity against 4 representing strains using the Kirby-Bauer disk diffusion method. Minimal inhibitory concentration (MIC) was determined by measuring the diameter of the inhibition zone using concentrations between 250 and 0.004 µg/mL. RESULTS: MIC of derivatives 2, 3, and 4 showed potent antimicrobial activity against gram-positive and gram-negative bacteria. The effective concentrations were 0.860 µg/mL or lower. MIC for compounds 5-11 were between 120 and 515 µg/mL against Escherichia coli and Staphylococcus aureus, and substituted hydrazinoquinolones 7-10 showed poor antibacterial activity against gram-positive and gram-negative bacteria compared with other quinolones. CONCLUSION: Compounds obtained by modifications on C-7 of norfloxacin with the acetylated piperazinyl, halogen atoms, and substituted hydrazinyl showed good in vitro activity - some even better than the original compound.

Fluoroquinolonas: perspectivas no antibacterianas / Fluoroquinolones: non-antibacterial properties

Las fluoroquinolonas son agentes quimioterapéuticos con potente actividad biológica siendo la estructura de los ácidos 4-quinolona-3-carboxílicos privilegiada ya que contiene diferentes sitios para la funcionalización, permitiendo ampliar su uso en la práctica clínica por sus actividades antifúngicas, antivirales y anticancerosas. Las variaciones estructurales en quinolonas ha resultado en una primera, segunda, tercera y cuarta generación de fármacos por lo que es recomendable continuar modificando estructuras existentes en formas novedosas para generar compuestos con propiedades biológicas y farmacológicas deseables (AU)

Fluoroquinolones are a class of well-established chemotherapeutic agents with a potent biological activity being the structure of 4-quinolone-3-carboxilic acids privileged because it contains different sites for functionalization allowing expand its use in clinical practice for their antifungal, antiviral and anticancer activities. Quinolones structural changes have resulted in a first, second, third and fourth generation of drugs so it is advisable to continue modifying existing structures in new ways to generate compounds with desirable biological and pharmacological properties (AU)