Dereplication of 4-Quinolone Alkaloids from Waltheria Indica (Malvaceae) Tissues Using Molecular Network Tools.

Waltheria indica (Malvaceae) is a plant popularly used in folk medicine by traditional African and indigenous communities, and in various countries worldwide, to treat general inflammation. Several biological activities of this plant have been reported, including acetylcholinesterase inhibition and potential anti-human immunodeficiency virus (HIV), antinociceptive, analgesic, antifungal, anticancer, anti-inflammatory, leishmanicidal, trypanocidal, antioxidant, and antibacterial activities. The chemical profile of Waltheria indica was assessed by dereplication analysis using UPLC-MS/MS, and data acquisition was performed using chemoinformatics tools, such as Mass Spectrometry-Data Independent AnaLysis (MS-DIAL) and MS-FINDER softwares. The preprocessed data were sent to the GNPS to build a feature-based molecular network (FBMN). Thirty-three 4-quinolone alkaloids were annotated in the extracts and fractions of stems and roots, whereas 12 were annotated in the extracts and fractions of flowers and leaves. This represents an inaugural chemical investigation study employing UPLC-Q-TOF-MS/MS analysis, along with a molecular network approach, within this species and genus.

Insights into nucleoside hydrolase from Leishmania donovani inhibition: A new bioaffinity chromatography-based screening assay and docking studies.

Leishmaniasis, a group of neglected infectious diseases, encompasses a serious health concern, particularly with visceral leishmaniasis exhibiting potentially fatal outcomes. Nucleoside hydrolase (NH) has a fundamental role in the purine salvage pathway, crucial for Leishmania donovani survival, and presents a promising target for developing new drugs for visceral leishmaniasis treatment. In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(ß-d-Ribofuranosyl)-4-quinolone derivative) was used as a model to validate the established method in inhibitor recognition. Screening of three additional derivatives of 1-(ß-d-Ribofuranosyl)-4-quinolone led to the discovery of novel inhibitors, with compound 2a exhibiting superior inhibitory activity (Ki = 23.37 ± 3.64 µmol/L) compared to the employed model inhibitor. Docking and Molecular Dynamics studies provided crucial insights into inhibitor interactions at the enzyme active site, offering valuable information for developing new LdNH inhibitors. Therefore, this study presents a novel screening assay and contributes to the development of potent LdNH inhibitors.

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone.

In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone-carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 µM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 µM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 µM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.

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)

Bacteriemia por Capnocytophaga spp.: a propósito de dos casos / Bacteriemia due to Capnocytophaga spp.: two cases

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Clinical and Microbiological Characteristics of Spontaneous Bacterial Peritonitis (SBP) in A Recent Five Year Period / 대한간학회지

BACKGROUNDS/AIMS: Recently, treatment failure with the third generation of cephalosporin was increasingly noted in patients with spontaneous bacterial peritonitis (SBP). We therefore were to evaluate the pattern of antibiotic resistance and its clinical significance. METHODS: We retrospectively analyzed 580 episodes of SBP occurring between 1995 and 1999. There were 87 episodes of SBP in 1995, 222 in 1998, and 271 in 1999. The pattern of isolated organisms and antibiotic resistance, and prognostic factors for survival, were analyzed. RESULTS: Microorganisms were isolated in 41% of total episodes. The three most frequently isolated organisms were E. coli (48%), K. pneumoniae (15%), and Aeromonas (8%). The percentage of resistant strains to cefotaxime (9%, 14%, 32%) and ciprofloxacin (13%, 21%, 32%) significantly increased. The proportion of E. coli producing extended spectrum beta-lactamase (ESBL) also increased significantly (0%, 16%, 33%). The need of secondary antibiotics such as imipenem due to treatment failure was significantly increased from 0% in 1995 to 33% in 1999. Overall in-hospital mortality, however, was not changed (20%, 20%, 24%, respectively). The factor affecting early mortality was renal failure at diagnosis. Prognostic factors for long-term survival were the presence of associated malignancy and ESBL-producing microorganisms. CONCLUSION: Microorgansims resistant to third generation cephalosporin and quinolone were increasingly isolated over the 5 years in patients with SBP. Measures to prevent in-hospital spread of resistant strains and indiscreet use of antibiotics should therefore be instituted.