MIC Values Research Articles

Design, synthesis, biological evaluation study of spirocyclic POM analogues as novel MmpL3 anti-tubercular agent

We present the development of a phenyl oxazole methyl (POM) core structure with spirocyclic derivatives as part of our efforts to discover innovative anti-tuberculosis agents. Derivatives of spirocyclic POM were synthesized and evaluated for their inhibitory effects on M.tuberculosis (M. tb) H37Rv. Notably, compound 5c displayed potent anti-tubercular activity with MIC value of 0.206 μM in culture broth medium. Furthermore MIC values of compound 5c against DS/MDR/pre-XDR clinical isolates ranged from 0.34 to 0.68 μg/mL, 0.17 to 0.68 μg/mL, and 0.17 to 0.34 μg/mL, respectively. Also, compound 5c with favorable ADME and PK properties was not cytotoxic to THP-1 human cells. Based on the spontaneous mutant generation, we have identified the target of compound 5c to be MmpL3. The computational docking study suggested its plausible binding mode against MmpL3. There is no approved drug targeting this target yet, and the outcomes of the presented research will contribute to the future discovery of novel anti-tuberculosis drugs.

Tityus stigmurus-Venom-Loaded Cross-Linked Chitosan Nanoparticles Improve Antimicrobial Activity.

The rapid resistance developed by pathogenic microorganisms against the current antimicrobial pool represents a serious global public health problem, leading to the search for new antibiotic agents. The scorpion Tityus stigmurus, an abundant species in Northeastern Brazil, presents a rich arsenal of bioactive molecules in its venom, with high potential for biotechnological applications. However, venom cytotoxicity constitutes a barrier to the therapeutic application of its different components. The objective of this study was to produce T. stigmurus-venom-loaded cross-linked chitosan nanoparticles (Tsv/CN) at concentrations of 0.5% and 1.0% to improve their biological antimicrobial activity. Polymeric nanoparticles were formed with a homogeneous particle size and spherical shape. Experimental formulation parameters were verified in relation to mean size (<180 nm), zeta potential, polydispersity index and encapsulation efficiency (>78%). Tsv/CN 1.0% demonstrated an ability to increase the antimicrobial venom effect against Staphylococcus aureus bacteria, exhibiting an MIC value of 44.6 μg/mL. It also inhibited different yeast species of the Candida genus, and Tsv/CN 0.5% and 1.0% led to a greater inhibitory effect of C. tropicalis and C. parapsilosis strains, presenting MIC values between 22.2 and 5.5 µg/mL, respectively. These data demonstrate the biotechnological potential of these nanosystems to obtain a new therapeutic agent with potential antimicrobial activity.

Unveiling the therapeutic potential of Haloxylon articulatum extract: a comprehensive study on its phytochemical composition, antioxidant, antifungal, and antibacterial activities

ABSTRACT Haloxylon articulatum, commonly known as the salt tree have diverse medicinal benefits. The phytochemical content, antioxidant, antibacterial, and antifungal properties of the methanolic extract were assessed. The extract demonstrated a high concentration of flavonoids and phenolic components, with a Total Flavonoid Content (TFC) of 186 ± 3 µg QE/mg extract and a Total Phenolic Content (TPC) of 188.1 ± 0.4 µg GAE/mg extract. Bioactive substances with anti-inflammatory and antioxidant qualities, such as quercetin, rutin, chrysin, and caffeic acid, were detected by LC-MS analysis. Through IC50 values of 28.88, 14.13, and 23.03 µg/mL for DPPH, β-carotene, and ABTS tests, respectively, the extract demonstrated considerable antioxidant activity. Antibacterial activity was reported against Escherichia coli and Staphylococcus aureus, with bactericidal effects indicated by MIC and MBC values. The extract also exhibited potent antifungal activity against Thielaviopsis paradoxa and Alternaria sp. These results suggest that H. articulatum extract is a promising source of natural antioxidants and antimicrobial agents with potential therapeutic applications.

Synthesis and antimicrobial activity of benzoxazine/benzothiazine appended 1,2,3-triazole hybrids

In the present context to rationalize the search for new effective antimicrobial agents against the infections caused by microbes, a series of benzoxazine/benzothiazine appended 1,2,3-triazole hybrids were designed and synthesized via click reaction with ingredients of two or more bioactive moieties through the concept of molecular hybridization. Various spectral techniques such as FTIR, 1H NMR, 13C NMR, 2D NMR and HRMS were utilized for structural elucidation of the synthesized hybrids. The serial dilution method was employed for performing the antimicrobial activity of synthesized triazoles against four bacterial (S. aureus, B. subtilis, E. coli, K. pneumoniae) and two fungal (C. albicans, A. niger) strains. The antibacterial results demonstrated that a couple of hybrids show noteworthy outcomes related to standard medication. Compound 4r was indicated great action against E. coli with MIC values 0.0259 µmol/mL. Based on outcomes of antibacterial activity, molecular docking study was carried out with E. coli DNA gyrase to understand the binding behavior. To check out the drug-likeness, in silico ADME (Absorption, Distribution, Metabolism and Excretion) studies of synthesized hybrids were also analyzed and found that compounds can be developed as potential oral drug candidates.

Repurposing antiparasitic N,N'-aliphatic diamine derivatives as promising antimycobacterial agents.

In previous studies, we demonstrated the potent activity of a library of 25 N,N'-disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non-pathogenic species, and the non-tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web-based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies.

A new tetrahydroxybenzophenone from a marine-associated fungus of penicillium sp. and its potential antibacterial activity

Penicillium species are renowned for their ability to produce a wide range of secondary metabolites with medicinal properties. In this study, compounds 1-10 were isolated from Penicillium sp. Z-16, of which compound 1 is a new benzophenone derivative named methyl 2-(2,6-dihydroxy-4-methylbenzoyl)-4,5-dihydroxy-3-methoxybenzoate. The chemical structure of 1 was determined through comprehensive spectroscopic analysis, including 1D, 2D NMR (HMBC, HSQC) and HRESIMS. In addition, six other known compounds (11-16) were isolated and identified from Penicillium sp. T-5-1. The antimicrobial activity tests demonstrated that compound 1 was moderately active against Candida albicans with a MIC value of 125 μg/mL, while compound 2 showed a MIC value of 62.5 μg/mL against Staphylococcus aureus.

Vitamin B6 appended polypyridyl Co(III) complexes for photo-triggered antibacterial activity.

Three novel polypyridyl-Co(III)-vitamin B6 complexes viz., [Co(CF3-phtpy)(SBVB6)]Cl (Co1), [Co(anthracene-tpy)(SBVB6)]Cl (Co2), [Co(NMe2-phtpy)(SBVB6)]Cl (Co3), where 4'-(4-(trifluoromethyl)phenyl)-2,2':6',2''-terpyridine = CF3-phtpy, 4'-(anthracen-9-yl)-2,2':6',2''-terpyridine = anthracene-tpy;, 4-([2,2':6',2''-terpyridin]-4'-yl)-N,N-dimethylaniline = NMe2-phtpy, (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol = H2SBVB6 was successfully developed for aPDT (antibacterial photodynamic therapy) applications. Co1-Co3 exhibited an intense absorption band at ca. 435-485 nm, which is attributed to ligand-to-metal charge transfer and was beneficial for antibacterial photodynamic therapy. The distorted octahedral geometry of the complexes with CoIIIN4O2 core was evident from the DFT study. The visible light absorption ability and good photo-stability of Co1-Co3 made them good photosensitizers for aPDT. Co1-Co3 displayed significant antibacterial responses against gram-positive (S. aureus) and gram-negative (E. coli) bacteria upon light exposure (10 J cm-2, 400-700 nm) and showed MIC values between 0.01-0.005 µg mL-1. The aPDT activities of these complexes were due to their ability to damage bacterial cell membranes via ROS generation. Overall, this study shows the photo-triggered ROS-mediated bacteria-killing potential of Co(III) complexes.

Lentil Extract-Mediated Ag QD Synthesis: Predilection for Albumin Protein Interaction, Antibacterial Activity, and Its Cytotoxicity for Wi-38 and PC-3 Cell Lines.

Recent focus has been directed toward semiconductor nanocrystals owing to their unique physicochemical properties. Nevertheless, the synthesis and characterization of quantum dots (QDs) pose considerable challenges, limiting our understanding of their interactions within a biological environment. This research offers valuable insights into the environmentally friendly production of silver quantum dots (Ag QDs) using lentil extract and clarifies their distinct physicochemical characteristics, previously unexplored to our knowledge. These findings pave the path for potential practical applications. The investigation of the phytochemical-assisted Ag QDs' affinity for BSA demonstrated modest interactions, as shown by the enthalpy and entropy changes as well as the associated Gibbs free energy during their association. Steady-state and time-resolved fluorescence spectroscopy further demonstrated a transient effect involving dynamic quenching, predominantly driven by Forster resonance energy transfer. Additionally, the study highlights the potential broad-spectrum antibacterial activity of Ag QDs (<5 nm, a zeta potential of -3.04 mV), exhibiting a remarkable MIC value of 1 μg/mL against Gram-negative bacteria (E. coli) and 1.65 μg/mL against Gram-positive bacteria (S. aureus). They can readily enter cells and tissues due to their minuscule size and the right chemical environment. They cause intracellular pathway disruption, which leads to cell death. This outcome emphasizes the distinctive biocompatibility of the green-synthesized Ag QDs, which has been confirmed by their MTT assay-based cytotoxicity against the PC-3 and Wi-38 cell lines.

From cornfield to catalyst support: Eco-friendly synthesis of Cu/CuO nanoparticles, immobilization on the waste corn husk fibers, photocatalytic exploration and bioactivity evaluation

This study presents an innovative approach to eco-friendly synthesis and utilization of copper nanoparticles (CuNPs) for photocatalytic applications, employing waste corn husk fibers as sustainable catalyst support. The synthesis of CuNPs was achieved through a green synthesis method utilizing myrtle extract. Subsequently, the remarkable photocatalytic activity of the CuNPs explored (76% removal efficiency of Crystal Violet), showcased their potential in environmental remediation applications. Furthermore, the immobilization of CuNPs onto waste corn husk fibers was investigated, aiming to develop a novel composite material with enhanced catalytic performance. A distinctive approach was introduced by immobilizing CuNPs onto fibers derived from corn husks, and waste biomass material, leading to a significant enhancement in photocatalytic efficiency, surpassing 95.1%. Furthermore, bioactivity evaluation studies revealed the significant antioxidant, antidiabetic, DNA fragmentation, cell viability, antibiofilm and antimicrobial properties of CuNPs. The antioxidant ability was determined at 100 mg/L as 87.12%. The most powerful antimicrobial activity of CuNP was found as a MIC value of 8 mg/L against E. faecalis. The cell viability inhibition of CuNP was 90.05% at 20 mg/L. CuNP exhibited biofilm inhibition activity at different concentrations. The antibiofilm ability was investigated against Staphylococcus aureus compared to Pseudomonas aureginosa. While the DNA cleavage activity of CuNP observed double-strand breaks at 50 and 100 mg, complete fragmentation occurred at 200 mg concentrations. The bioactivity of the synthesized CuNPs shed light on their potential biomedical applications. The synthesized CuNPs are characterized using various analytical techniques to elucidate their structural and morphological properties. Fourier-transform infrared (FTIR) analysis provided insights into the chemical composition and surface properties of the synthesized materials. EDS analysis confirmed their successful integration into waste corn husk fibers. Overall, this interdisciplinary study highlights the potential of CuNPs immobilized on waste corn husk fibers for addressing environmental pollution, advancing sustainable technologies and paving the way for the development of efficient catalysts with diverse functionalities.

Polyvinyl alcohol-chitosan based oleanolic acid nanofibers against bacterial infection: In vitro studies and in vivo evaluation by optical and laser Doppler imaging modalities

The present work focuses on the fabrication of polyvinyl alcohol-chitosan-loaded oleanolic acid-nanofibers (PVA-CS-OLA-NFs) for bacterial infection. The prepared PVA-CS-OLA-NFs were characterized for contact angle, SEM, AFM, XRD, FTIR, and TGA. The solid-state characterization and in vitro performance evaluation of nanofibers reveal consistent interconnection and diameters ranging from 102 ± 9.5 to 386 ± 11.6 nm. The nanofibers have a flat surface topography and exhibit efficient drug entrapment. Moreover, the in vitro release profile of PVA-CS-OLA-NFs was found to be 51.82 ± 1.49 % at 24 h. Furthermore, the hemocompatibility study showed that the developed PVA-CS-OLA-NFs are non-hemolytic to human blood. The PVA-CS-OLA-NFs demonstrate remarkable antibacterial capabilities, as evidenced by their MBC and MIC values, which range from 128 and 32 μg/mL, against the strains of S. aureus. The in-vivo fluorescence optical imaging showed the sustained PVA-CS-OLA-NFs release at the wound site infected with S. aureus for a longer duration of time. Moreover, the PVA-CS-OLA-NFs showed superior wound healing performance against S. aureus infected wounds compared to the marketed formulation. Further, the laser Doppler imaging system improved oxygen saturation, blood supply, and wound healing by providing real-time blood flow and oxygen saturation information.

An Engineered Nisin Analogue with a Hydrophobic Moiety Attached at Position 17 Selectively Inhibits Enterococcus faecium Strains.

Antibiotic resistance is one of the most challenging global public health concerns. It results from the misuse and overuse of broad-spectrum antibiotics, which enhance the dissemination of resistance across diverse bacterial species. Antibiotics like nisin and teixobactin do not target an essential protein and employ a dual mode of action antibacterial mechanism, thereby being less prone to induce resistance. There is a need for the development of a potent narrow-spectrum dual-mode-acting antibiotic against human pathogens. Using nisin, a lantibiotic with potent antimicrobial activity against many pathogens, as a template, the unnatural amino acid azidohomoalanine was introduced at selected positions and subsequently modified using click chemistry with 14 alkyne-moiety containing tails. A novel nisin variant, compound 47, featuring a benzyl group-containing tail, exhibited potent activity against various (drug-resistant) E. faecium strains with an MIC value (3.8 mg/L) similar to nisin, whereas its activity toward other pathogens like Staphylococcus aureus and Bacillus cereus was significantly reduced. Like nisin, the mode of action of compound 47 results from the inhibition of cell wall synthesis by binding to lipid II and nisin-lipid II hybrid-pore formation in the outer membrane. The resistance of compound 47 against proteolytic degradation is markedly enhanced compared to nisin. Like nisin, compound 47 was hardly hemolytic even at a very high dose. Collectively, a modified nisin variant is presented with significantly enhanced target organism specificity and stability.

Novel Teixobactin Analogues Show Promising In Vitro Activity on Biofilm Formation by Staphylococcus aureus and Enterococcus faecalis

The treatment of infections caused by biofilm-forming organisms is challenging. The newly discovered antibiotic teixobactin shows activity against a wide range of biofilm-forming bacteria. However, the laborious and low-yield chemical synthesis of teixobactin complicates its further development for clinical application. The use of more easily synthesized teixobactin analogues may offer promise in this regard. In this article, three newly developed analogues were tested for efficacy against Staphylococcus aureus and Enterococcus faecalis. Minimum inhibitory and -bactericidal concentrations were investigated. MIC values for S. aureus and E. faecalis ranged from 0.5–2 and 2–4 μg/mL, respectively. Moreover, the ability of the analogues to prevent biofilm formation and to inactivate bacterial cells in already established S. aureus biofilm on medical grade materials (PVC and PTFE) used in the production of infusion tubing and catheters were also tested. The analogues showed an ability to prevent biofilm formation and inactivate bacterial cells in established biofilms at concentrations as low as 1–2 μg/mL. Confocal laser scanning microscopy showed that the most promising analogue (TB3) inactivated S. aureus cells in a preformed biofilm and gave a reduction in biovolume. The relative ease of synthesis of the analogues and their in vitro efficacy, makes them promising candidates for pharmaceutical development.Graphical

Antimicrobial Dihydroflavonols and Isoflavans Isolated from the Root Bark of Dalbergia gloveri.

Three new dihydroflavonols, gloverinols A-C (1-3), a new flavon-3-ol, gloverinol D (4), two new isoflavans, gloveriflavan A (5) and B (6), and seven known compounds were isolated from the root bark of Dalbergia gloveri. The structures of the isolates were elucidated by using NMR, ECD, and HRESIMS data analyses. Among the isolated compounds, gloverinol B (2), gloveriflavan B (6), and 1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4-hydroxyphenyl)-1-propanone (10) were the most active against Staphylococcus aureus, with MIC values of 9.2, 18.4, and 14.2 μM, respectively.

Assessing the structural, antibacterial, and dissolution properties of 1:1 doxycycline/β-cyclodextrin complexes

A 1:1 β-cyclodextrin (βCD) inclusion complex with doxycycline (DO) as the guest molecule was prepared using kneading (KN) and coprecipitation (CoP) methods, along with a physical mixture (PM) . The complex was characterized through FTIR, ¹H NMR, UV–Vis spectroscopy, and DSC analysis. Semi-empirical quantum mechanical calculations confirmed the inclusion of DO within βCD's hydrophobic cavity. The formation constant, determined by a modified Benesi-Hildebrand equation at 25 °C, was 116.22 M⁻¹ for the βCD-DO complex. Dissolution studies revealed that the CoP method significantly enhanced DO's dissolution kinetics compared to the KN, PM methods, and free DO, highlighting CoP's effectiveness. Molecular docking indicated a stable βCD-DO complex, with binding energies from -5.9570 to -6.1423 kcal/mol, driven by hydrophilic and hydrophobic interactions. Antibacterial testing against E. coli, P. aeruginosa, S. aureus, B. cereus, and B. subtilis showed CoP had the highest efficacy, with MIC values of 5–10 µg/ml and MBC values of 10–20 µg/ml, better than KN, DO, and βCD.

Discovery of membrane-targeting amphiphilic honokiol derivatives containing an oxazolethione moiety to combat methicillin-resistant Staphylococcus aureus (MRSA) infections

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2–4 μg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections.

Pestiorosins A-F, New Papulacandins Isolated from the Fungus Pestalotiopsis rosea YNJ21.

Six previously unreported papulacandins, namely pestiorosins A-F (1-6), were isolated from the fermentation products of the fungus Pestalotiopsis rosea YNJ21 isolated from the fruitbody of Amanita exitialis. The structures of these compounds, along with a known compound called pestiocandin (7), were determined using MS, NMR data, and modified Mosher's method. All compounds exhibited significant antifungal activity against Candida albicans, with MIC values ranging from 0.06 to 2.00 μg/mL. In terms of cytotoxicity assays, compounds 3 and 6 demonstrated moderate inhibitory activity against human breast cancer MCF-7 cells with IC50 values of 24.50 and 16.83 μM, respectively. On the other hand, compound 7 displayed similar levels of inhibitory activity against mice microglial BV2 cells with an IC50 value of 24.51 μM.

Assessment of antioxidant, antidiabetic, and antimicrobial properties of hybrid mushroom strains derived through intergeneric hybridization between Pleurotus sajor-caju and Calocybe indica

Our present study aims to evaluate the biological activities of the six hybrid mushrooms (APS) obtained through the protoplast fusion technique between two mushrooms Calocybe indica and Pleurotus sajor-caju, in our previous study. Antioxidant activity of hybridized mushroom samples was determined by the free radical scavenging method, using DPPH radical, Superoxide radical, and Hydroxyl radical. Additionally, all the mushroom extract has shown a good amount of total phenolic content, and total flavonoid content and also has potent Ferric reducing antioxidant power. The Total phenolic content, Total flavonoid content, and Ferric reducing antioxidant power were estimated. Six constituents: gallic acid, catechin, protocatechuic acid, p-hydroxybenzoic acid, p-coumaric acid, and cinnamic acid were identified by UHPLC. The MIC values, zone of inhibition, growth kinetic, and scanning electron microscopy (SEM) were performed to establish the antimicrobial efficacy. The tested samples exhibited antimicrobial activity against selected microorganisms Staphylococcus aureus, Klebsiella pneumoniae, Bacillus subtilis, Pseudomonas aeruginosa. A clear morphological change was observed under SEM when Bacillus subtilis and Pseudomonas aeruginosa were treated with APS-4 and APS-3 mushroom extracts. The ability to inhibit carbohydrate hydrolyzing enzymes such as α-amylase and α-galactosidase has also been studied to explore antidiabetic properties. The inhibitory activity of α-glucosidase was APS-4 reflected a very prominent result with the lowest IC50 value i.e.,118.058 ± 1.515, APS-2 and APS-6 showed almost similar IC50 values. α – galactosidase inhibitory activity of APS-4 and APS-6 exhibit better results than other strains.

Diterpenoids of Caryopteris trichosphaera W. W. Sm. inhibiting MRSA and VRE in vitro and in vivo

Ethnopharmacological relevanceCaryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. Aim of the studyTo investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. Materials and methodsBioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. ResultsSix antibacterial diterpenoids against MRSA and VRE with MIC values 4–32 μg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. ConclusionsThe results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.

The volatile organic compounds detection in MDR Gram-negatives antimicrobial susceptibility testing: Results from a four-month laboratory experience

Systemic bacterial infections represent a significant clinical challenge due to the increasing resistance rate towards antimicrobials. An essential key to controlling antimicrobial resistance spread is to administer targeted therapy after a precise minimum inhibitory concentration reporting. Among the available fast technologies for antimicrobial susceptibility testing (AST), the VITEKⓇ REVEAL™ (Biomerieux, Florence, Italy) proposes volatile organic compounds (VOC) colourimetric arrays to discriminate between susceptible and resistant Gram-negative isolates directly from positive blood cultures. We evaluated this methodology during a four-month laboratory experience on 40 positive blood culture samples, reporting a comparison to standard culture-based methods. The protocol revealed an essential agreement of 100 % between the conventional and the experimental procedures, while the categorical agreement resulted in 97.5 % due to one very major error (VME) for meropenem/vaborbactam in K. pneumoniae. Although further studies will be necessary to investigate its performance on rare microorganisms, the VITEKⓇ REVEAL™ demonstrated an optimal sensitivity in defining MIC values for multi-drug resistant (MDR) microorganisms. These results encourage the application of the method in all high-risk epidemiological areas, confirming the effectiveness of VOC detection in monitoring bacterial susceptibility profiles.

Design and Synthesis of Isatin-Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In-vitro and In-silico Evaluations.

In pursuit of potential chemotherapeutic alternates to combat severe tuberculosis infections, novel heterocyclic templates derived from clinically approved anti-TB drug isoniazid and isatin have been synthesized that demonstrate potent inhibitory action against Mycobacterium tuberculosis, and compound 4i with nitrophenyl motif exhibited the highest anti-TB efficacy with a MIC value of 2.54 μM/ml. Notably, the same nitro analog 4i shows the best antioxidant efficacy among all the synthesized compounds with an IC50 value of 37.37 μg/ml, suggesting a synergistic influence of antioxidant proficiency on the anti-TB action. The titled compounds exhibit explicit binding affinity with the InhA receptor. The befitting biochemical reactivity and near-appropriate pharmacokinetic proficiency of the isoniazid conjugates is reflected in the density functional theory (DFT) studies and ADMET screening. The remarkable anti-TB action of the isoniazid cognates with marked radical quenching ability may serve as a base for developing multi-target medications to confront drug-resistant TB pathogens.