Broad-spectrum Activity Research Articles

Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors.

Cancer is a leading threat to humankind, accounting for nearly one million deaths in 2018, and the expected number of cancer-related deaths in 2040 is more than 16 million. The most common causes of cancer deaths are lung, colorectal, stomach, liver and breast cancer, while the highest number of new cancer cases belong to lung, breast, colorectal, prostate, stomach and liver cancer. PARP-1 is an enzyme that plays an important role in DNA repair, cell propagation/survival and death due to its influence on numerous biological processes. Quinazolinones represent an important scaffold in medicinal chemistry and have a broad spectrum of biological activities. In this study, we have synthesized quinazolinones by reaction of 2-aminobenzamide and substituted aldehydes. Molecular docking studies of synthesized compounds were performed for their PARP-1 binding affinities using Schrodinger 2016 software. In silico ADME studies were also performed for the synthesized compounds using the QikProp tool of Schrodinger software. Results of molecular docking studies indicated that synthesized quinazolinones had a good affinity towards active site of PARP-1 and compound 4 had the best docking score (-10.343). Results of ADME studies indicated the drug-like properties of synthesized compounds, which make them suitable drug candidates. All the synthesized compounds have a better docking score than niraparib (-9.05). Further, the synthesized compounds have a favorable ADME profile. Therefore, they may serve as important leads in discovering PARP-1 inhibitors.

Heteroaromatization of Coumarin Part I: Design, Synthesis, Reactions, Antitumor Activities of Novel Pyridine and Naphthyridine Derivatives.

A novel series of chromen-3-yl-pyridine moieties were synthesized. IR, NMR, and MS spectroscopy were used to confirm the structure of these novel compounds and study antitumor activity of these compounds. The structure-activity relationship investigation demonstrated that 2,4-diamino- 5-(3-methoxyphenyl)-7-(2-oxo-2H-chromen-3-yl)-1,8-naphthyridine-3-carbonitrile (16), naphthyridine- 3-carbonitrile derivatives 17, 18 and pyrido[2,3-d]pyrimidine derivative 12 were found to be more effective, while compounds 5a,b, 9c, 11, 13 and 14 showed moderate activity for antitumor activities. The objective was to design a series of new chromen-3-yl-pyridine and pyrido[2,3-d]pyrimidine derivatives and study the antitumor of these compounds. The condensation reaction of 3-acetyl-2H-chromen-2-one with 3-methoxy benzaldehyde and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate and acetic acid under reflux to give the corresponding chromen-3-yl pyridine-3-carbonitrile derivatives. In this study, the antitumor activity of the synthesized compounds chromen-3-yl-pyridine derivatives has been determined for the broad spectrum of cytotoxic activity toward the investigated three cell lines and 5-Fluorouracil, as reference drugs. A series of new chromen-3-yl-pyridine and pyrido[2,3-d]pyrimidine derivatives were synthesized in this work. All compounds were evaluated for cytotoxic activity.

SYNTHESIS, CHARACTERIZATION & BIOLOGICAL EVALUATION OF SOME FLUOROQUINOLONE DERIVATIVES AS ANTIMICROBIAL AGENTS

Fluoroquinolones, a class of synthetic antibacterial agents, have gained significant attention due to their broad-spectrum activity against various bacterial pathogens. However, the emergence of resistance to conventional fluoroquinolones underscores the necessity for novel derivatives with enhanced efficacy and reduced resistance profiles. The synthesis of fluoroquinolone derivatives involves structural modifications aimed at improving antimicrobial activity, pharmacokinetic properties, and minimizing adverse effects. Various synthetic routes, including modification of the quinolone core structure, substitution of fluorine atoms, and introduction of diverse functional groups, have been explored to tailor the properties of these derivatives. Characterization techniques such as infrared spectroscopy (IR) has been employed to elucidate the chemical structures and confirm the purity of synthesized compounds. Biological evaluation encompasses in vitro and in vivo studies to assess the antimicrobial activity, cytotoxicity, and pharmacological profiles of fluoroquinolone derivatives. These evaluations provide crucial insights into the therapeutic potential, mechanism of action, and safety profile of novel compounds.

Flavonoids isolated from Vismia macrophylla Kunth against resistant bacteria.

The antimicrobial activity of Vismia macrophylla extract is reported in the literature; however, little is known about the presence of phenolic compounds and their antimicrobial activity in this species. This study aimed to isolate phenolic compounds with antimicrobial action from the leaves of V. macrophylla. The ethanolic extract (VmL-Et) was submitted to sephadex column separation, and some fractions were submitted to derivatization with BSTFA and analysed by GC-MS. This study indicated the presence of the catechin, osajaxanthone, quercetin, quercitrin, and glucodistylin. Of these, osajaxanthone, quercetin, quercitrin, and glucodistylin were isolated and identified by spectroscopic techniques. VmL-Et, quercetin, quercitrin, glucodistylin, and maslinic acid, were tested against the Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis. The results showed broad spectrum action of the extract Vm-Et, glucodistylin and quercitrin. The species V. macrophylla occurring in the Brazilian biome showed potential for obtaining phenolic compounds that can help combat microbial resistance.

Design, Synthesis, and Antifungal Evaluation of Diverse Heterocyclic Hydrazide Derivatives as Potential Succinate Dehydrogenase Inhibitors.

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 μg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 μg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 μg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 μM, respectively, which were superior to that of boscalid (IC50 = 2.38 μM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.

Suppression of anthracnose disease by orsellinaldehyde isolated from the mushroom Coprinus comatus.

Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on MS and NMR analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with FDA and PI demonstrated that the compound is fungicidal. The post-harvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.

Investigation of the Odilorhabdin Biosynthetic Gene Cluster Using NRPS Engineering.

The recently identified natural product NOSO-95A from entomopathogenic Xenorhabdus bacteria, derived from a biosynthetic gene cluster (BGC) encoding a non-ribosomal peptide synthetase (NRPS), was the first member of the odilorhabdin class of antibiotics. This class exhibits broad-spectrum antibiotic activity and inspired the development of the synthetic derivative NOSO-502, which holds potential as a new clinical drug by breaking antibiotic resistance. While the mode of action of odilorhabdins was broadly investigated, their biosynthesis pathway remained poorly understood. Here we describe the heterologous production of NOSO-95A in Escherichia coli after refactoring the complete BGC. Since the production titer was low, NRPS engineering was applied to uncover the underlying biosynthetic principles. For this, modules of the odilorhabdin NRPS fused to other synthetases were co-expressed with candidate hydroxylases encoded in the BGC allowing the characterization of the biosynthesis of three unusual amino acids and leading to the identification of a prodrug-activation mechanism by deacylation. Our work demonstrates the application of NRPS engineering as a blueprint to mechanistically elucidate large or toxic NRPS and provides the basis to generate novel odilorhabdin analogues with improved properties in the future.

Photosensitizer-Amplified Antimicrobial Materials for Broad-Spectrum Ablation of Resistant Pathogens in Ocular Infections.

The emergence of multidrug resistant (MDR) pathogens and the scarcity of new potent antibiotics and antifungals are one of the biggest threats to human health. Antimicrobial photodynamic therapy (aPDT) combines light and photosensitizers to kill drug-resistant pathogens; however, there are limited materials that can effectively ablate different classes of infective pathogens. In the present work, a new class of benzodiazole-paired materials is designed as highly potent PDT agents with broad-spectrum antimicrobial activity upon illumination with nontoxic light. The results mechanistically demonstrate that the energy transfer and electron transfer between nonphotosensitive and photosensitive benzodiazole moieties embedded within pathogen-binding peptide sequences result in increased singlet oxygen generation and enhanced phototoxicity. Chemical optimization renders PEP3 as a novel PDT agent with remarkable activity against MDR bacteria and fungi as well as pathogens at different stages of development (e.g., biofilms, spores, and fungal hyphae), which also prove effective in an ex vivo porcine model of microbial keratitis. The chemical modularity of this strategy and its general compatibility with peptide-based targeting agents will accelerate the design of highly photosensitive materials for antimicrobial PDT.

Heterologous expression of frog antimicrobial peptide Odorranain-C1 in Pichia pastoris: Biological characteristics and its application in food preservation

To reduce food spoilage and deterioration caused by microbial contamination, antimicrobial peptides (AMPs) have gradually gained attention as a biological preservative. Odorranain-C1 is an α-helical cationic antimicrobial peptide extracted from the skin of frogs with broad-spectrum antimicrobial activity. In this study, we achieved the expression of Odorranain-C1 in Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) by employing DNA recombination technology. The recombinant Odorranain-C1 showed broad-spectrum antibacterial activity and displayed a minimum inhibitory concentration within the range of 8–12 μg.mL-1. Meanwhile, Odorranain-C1 exhibited superior stability and lower hemolytic activity. Mechanistically, Odorranain-C1 disrupted the bacterial membrane's integrity, ultimately causing membrane rupture and subsequent cell death. In tilapia fillets preservation, Odorranain-C1 inhibited the total colony growth and pH variations, while also reducing the production of total volatile basic nitrogen (TVB-N) and thiobarbituric acid (TBA). In conclusion, these studies demonstrated the efficient recombinant expression of Odorranain-C1 in P. pastoris, highlighting its promising utilization in food preservation.

Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach

Cordycepin, or 3′-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3′ position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3′ position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin’s mechanism of action.

The Ocular Chloramphenicol Story

Chloramphenicol eye drops and ointment are the most used ocular antibiotic worldwide. Chloramphenicol was discovered in 1947 and was only the third antibiotic to successfully be produced and only the first antibiotic suitable for large-scale commercial production. By the 1950s, the drug had been developed into drop and ointment forms. The broad spectrum of anti-bacterial activity of Chloramphenicol led to widespread use. Ocular Chloramphenicol remains an important weapon in the ophthalmic armamentarium despite emergence of evidence of possible side effects in the 1970s. This is a short review of the remarkable story of the discovery, development and tribulations of ocular Chloramphenicol. Keywords: History; Chloramphenicol Abbreviations: FDA: Food and Drug Administration

Characterization of antibiofilm compound from marine sponge Stylissa carteri.

The fouling phenomenon grabbed global attention and caused huge economic losses specifically in marine-related industries. Sessile behavior exposed the sponge to the risk of fouling. However, their bodies remained free from foulers, which were attributed to the chemical defense system. The objectives of this study were to determine the antibiofilm activity of the marine sponge, Stylissa carteri, and to characterize the isolated compound involved. The antibiofilm activity of S. carteri methanolic crude extract (MCE) and fractions was tested against biofilm-producing bacteria, Pseudomonas aeruginosa, using two different modes of crystal violet biofilm assays: preventive and detachment. Besides that, the disc-diffusion test was conducted to screen the antibacterial activity against gram-positive and gram-negative bacteria while a cytotoxicity assay was conducted on the HepG2 cell line. Bioassay-guided fractionation was carried out using vacuum liquid chromatography (VLC) and solid phase extraction using a C18 Sep-Pak Cartridge. The crystal compound was isolated and characterized through thin-layer chromatography (TLC), Fourier transform infrared (FTIR) spectroscopy, liquid chromatography-mass spectrometry (LCMS), and nuclear magnetic resonance (NMR) spectroscopy. The S. carteri MCE showed a promising result with a half-maximal inhibitory concentration (IC50) of 20.22μg/mL in the preventive assay, while no IC50 was determined in the detachment assay since all inhibitions < 50%. The S. carteri MCE exhibited broad-spectrum antibacterial activity and displayed a non-cytotoxic effect. Fraction 4 from MCE of S. carteri (IC50 = 2.40μg/mL) reduced the biofilm in the preventive assay at all concentrations and exhibited no antibacterial activity indicating the independence of antibiofilm from antibacterial properties. Based on the data obtained, an alkaloid named debromohymenialdisine (DBH) was identified from Fraction 4 of S. carteri MCE. In conclusion, S. carteri was able to reduce the establishment of the biofilm formed by P. aeruginosa and could serve as a prominent source of natural antifouling agents.

Michael Addition Reaction between Dehydroalanines and Phosphites Enabled the Introduction of Phosphonates into Oligopeptides.

A method for introducing a range of phosphonates into oligopeptides through a Michael addition reaction between dehydroalanine and phosphite is presented. The method offers a mild, cheap, and straightforward approach to peptide phosphorylation that has potential applications in chemical biology and medicinal chemistry. Moreover, the introduction of a phosphonate group into short antibacterial peptides is described to demonstrate its utility, leading to the discovery of phosphonated antibacterial peptides with potent broad-spectrum antibacterial activity.

A first-in-human clinical study investigating the safety and tolerability of stabilized hypochlorous acid in patients with chronic leg ulcers.

Biofilm infections in chronic wounds are common and pose a significant clinical challenge. This challenge was addressed by developing the SoftOx Biofilm Eradicator (SBE) composed of hypochlorous acid and acetic acid with strong broad-spectrum antimicrobial activity. First-in-human study investigating the safety and tolerability as primary endpoints, wound size effect and antimicrobial efficacy as secondary endpoints of SBE treatment in chronic leg wound patients. The study was divided into two: a randomized, double-blinded, Single Ascending Dose (SAD) phase (n=16 SBE; n=4 placebo), where patients were treated with SBE or saline (placebo) only once, followed by an open label, Multiple Ascending Dose (MAD) phase (n=8), where patients were treated with SBE once-daily or twice-daily over five days. Reporting according to CONSORT guidelines. SBE was safe and well-tolerated in chronic leg wound patients. There were no significant differences in pain during and after treatment with SBE or the placebo. The SBE treatment reduced bioburden in wounds compared to baseline, with 98 % and 49 % median reduction after SBE or placebo treatment, respectively. A dose dependent trend in absolute wound size reduction was observed in the MAD groups with a median (min, max) change of -2.99 (-14.25, -1.5) cm2 in the once-daily and -10.48 (-17.95, -0.38) cm2 in the twice-daily group, respectively. This study demonstrated the safe use of hypochlorous acid-based SBE in chronic leg wounds with promising trends of immediate antimicrobial action and beneficial effect on wound healing.

Dental Caries Management with Antibacterial Silver-Doped Prussian Blue Hydrogel by the Combined Effects of Photothermal Response and Ion Discharge.

Caries is a destructive condition caused by bacterial infection that affects the hard tissues of the teeth, significantly reducing the quality of life for individuals. Photothermal therapy (PTT) offers a noninvasive and painless treatment for caries, but the use of unsafe laser irradiance limits its application. To address this challenge, we prepared nanoparticles of silver ion-doped Prussian blue (AgPB), which was encased within cationic guar gum (CG) to form the antibacterial PTT hydrogel CG-AgPB with a photothermal conversion efficiency of 34.4%. When exposed to an 808 nm laser at a power density of 0.4 W/cm2, the hydrogel readily reached a temperature of over 50 °C in just 3 min, synchronized by the discharge of Ag+ ions from the interstitial sites of AgPB crystals, resulting in broad-spectrum and synergistic antibacterial activities (>99%) against individual oral pathogens (Streptococcus sanguinis, Streptococcus mutans, and Streptococcus sobrinus) and pathogen-induced biofilms. In vivo, CG-AgPB-mediated PTT demonstrated a capability to profoundly reduce the terminal number of cariogenic bacteria to below 1% in a rat model of caries. Given the outstanding biocompatibility, injectability, and flushability, this CG-AgPB hydrogel may hold promise as a next-generation oral hygiene adjunct for caries management in a clinical setting.

Secondary Structure Stabilization of Macrocyclic Antimicrobial Peptides via Cross-Link Swapping.

Lactam cross-links have been employed to stabilize the helical secondary structure and enhance the activity and physiological stability of antimicrobial peptides; however, stabilization of β-sheets via lactamization has not been observed. In the present study, lactams between the side chains of C- and N-terminal residues have been used to stabilize the β-sheet conformation in a short ten-residue analogue of chicken angiogenin-4. Designed using a combination of molecular dynamics simulations and Markov state models, the lactam cross-linked peptides are shown to adopt stabilized β-sheet conformations consistent with simulated structures. Replacement of the peptide side-chain Cys-Cys disulfide by a lactam cross-link enhanced the broad-spectrum antibacterial activity compared to the parent peptide and exhibited greater propensity to induce proinflammatory activity in macrophages. The combination of molecular simulations and conformational and biological analyses of the synthetic peptides provides a useful paradigm for the rational design of therapeutically active peptides with constrained β-sheet structures.

Insights into the biocontrol and plant growth promotion functions of Bacillus altitudinis strain KRS010 against Verticillium dahliae

BackgroundVerticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar “Zhongzhimian No. 2.”ResultsThe strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth.ConclusionsThis study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.

Antifungal activity of clove (Syzygium aromaticum) essential oil

Phytopathogenic fungi are responsible for approximately 70% of cultivated plant diseases. These fungi, which are capable of infecting any tissue of the plant and at any stage of its growth, can cause both qualitative and quantitative damage. Currently, the main means of combating plant diseases are: Cultural struggle, genetic struggle, biological struggle, Physical struggle and Chemical struggle which are generally very specific to each group. These solutions are not effective in the long term and can lead to the appearance of new pathogenic races through mutations or random and spontaneous parasexualities in addition to environmental pollution as well as residues may be present in the water, the ground and also in the finished product. Hence the need to find alternative solutions to continue to fight against diseases by minimizing the different methods of control mentioned above and by reducing the use of chemicals. In addition, the innovation of biofungicides has become a necessity for the benefit of humans and the environment. Essential oils have a very broad spectrum of activity, mainly due to their nature. The aim of this work is to study the antifungal activity of the essential oil of cloves on three phytopathogenic fungi: Fusarium oxysporum, Rhizoctonia solani, Alternaria alternata. Clove essential oil showed strong antifungal activity against the fungi tested.

De Novo Antimicrobial Peptide Design with Feedback Generative Adversarial Networks.

Antimicrobial peptides (AMPs) are promising candidates for new antibiotics due to their broad-spectrum activity against pathogens and reduced susceptibility to resistance development. Deep-learning techniques, such as deep generative models, offer a promising avenue to expedite the discovery and optimization of AMPs. A remarkable example is the Feedback Generative Adversarial Network (FBGAN), a deep generative model that incorporates a classifier during its training phase. Our study aims to explore the impact of enhanced classifiers on the generative capabilities of FBGAN. To this end, we introduce two alternative classifiers for the FBGAN framework, both surpassing the accuracy of the original classifier. The first classifier utilizes the k-mers technique, while the second applies transfer learning from the large protein language model Evolutionary Scale Modeling 2 (ESM2). Integrating these classifiers into FBGAN not only yields notable performance enhancements compared to the original FBGAN but also enables the proposed generative models to achieve comparable or even superior performance to established methods such as AMPGAN and HydrAMP. This achievement underscores the effectiveness of leveraging advanced classifiers within the FBGAN framework, enhancing its computational robustness for AMP de novo design and making it comparable to existing literature.

Tolerability of N-chlorotaurine in comparison with routinely used antiseptics: an in vitro study on chondrocytes.

Currently, povidone-iodine (PVP-I) and hydrogen peroxide (H2O2) are frequently used antiseptics in joint infections, but the cytotoxic effects of these solutions are already reported. N-chlorotaurine (NCT) shows a broad-spectrum bactericidal activity and is well tolerated in various tissues, but its effect on human chondrocytes is unknown. The purpose of this study was to assess the cytotoxic effect of NCT, PVP-I, and H2O2 on human chondrocytes compared to a control group in an in vitro setting to get first indications if NCT might be a promising antiseptic in the treatment of septic joint infections for the future. Chondrocytes extracted from human cartilage were incubated with various concentrations of NCT, PVP-I, and H2O2 for 5 and 30min respectively. EZ4U cell viability kit was used according to the manufacturer's recommendations determining cell viability. To assess cell viability based on their nuclear morphology, cells were stained with acridine-orange and identified under the fluorescence microscope. EZ4U kit showed after 5 and 30min of incubation a significant decrease in cell viability at NCT 1%, NCT 0.1%, PVP-I, and H2O2, but not for NCT 0.001% and NCT 0.01%. Acridine-orange staining likewise presented a significant decrease in vital cells for all tested solutions except NCT 0.001% and NCT 0.01% after 5 and 30min of incubation. Our results demonstrate that NCT is well tolerated by chondrocytes in vitro at the tested lower NCT concentrations 0.01% and 0.001% in contrast to the higher NCT concentrations 1% and 0.1%, PVP-I (1.1%), and H2O2 (3%), for which a significant decrease in cell viability was detected. Considering that the in vivo tolerability is usually significantly higher, our findings could be an indication that cartilage tissue in vivo would tolerate the already clinically used 1% NCT solution. In combination with the broad-spectrum bactericidal activity, NCT may be a promising antiseptic for the treatment of septic joint infections.