MIC Values Research Articles

Chemical Compositions and Antimicrobial and Mosquito Larvicidal Activities of the Leaf Essential Oils of Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast: Experimental and In Silico Approaches.

The current research describes a phytochemical analysis and antimicrobial activity of essential oils extracted from the leaves of two Vietnamese Annonaceae species Goniothalamus yunnanensis W.T.Wang and G. touranensis Ast. By the GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analyses, sesquiterpene hydrocarbons accounted for the highest percentage of 68.22 % in G. yunnanensis leaf essential oil with bicyclogermacrene (31.03 %) and (E)-caryophyllene (21.12 %) being the main compounds. G. touranensis leaf essential oil was dominated by monoterpene hydrocarbons (57.08 %) with p-cymene (19.95 %) and α-pinene (16.82 %) being the major compounds. By the microdilution broth susceptibility assay, two oil samples showed strong antibacterial effects on the Gram-positive bacteria Enterococcus faecalis ATCC51299, Staphylococcus aureus ATCC29213, and Bacillus cereus ATCC11778 with the MIC values of 16-64 μg/mL. They also inhibited the growth of the yeast Candida albicans ATCC 60193 with the same MIC value of 128 μg/mL. From the vector-based intervention approach, both oil samples showed strong mosquito larvicidal activity against four-instar larvae of Aedes aegypti and Ae. albopictus with the 24 h LC50 values of 16.75-27.60 μg/mL and 24 h LC90 values of 24.31-46.18 μg/mL. Docking results indicated that bicyclogermacrene and p-cymene exhibited the highest ΔG (binding affinity) values of -8.208 and -6.799 kcal/mol with the olfactory binding proteins (OBPs) of Ae. aegypti and Ae. albopictus, respectively.

Antimicrobial effect of (2-chloro-4-cyano-5-ethoxy-3,5-dioxopentan-2-yl) phosphonic acid against pathogenic bacteria and fungi

The synthesized organic compound ((2-chloro-4-cyano-5-ethoxy-3,5-dioxopentan-2-yl) phosphonic acid)) was evaluated against pathogenic microorganisms using agar well diffusion method. The results obtained reveled that, the diameters of inhibition zones were ranging between 24.0-36.3 mm for gram-negative bacteria, from 28.3 mm to 34.5 mm for gram-positive bacteria and between 18.2-20.3 mm for genus Candida. The MIC value 62.5 µg/mL showed that among gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa were the most sensitive to the compound compared to Acinetobacter baumannii and Klebsiella pneumoniae. Gram-positive bacteria (Staphylococcus aureus, Bacillus mesentericus and Bacillus subtilis) had the same sensitivity to the compound with 125 µg/mL as MIC value. Among fungal strains, Candida tropicalis with MIC value 62.5 µg/mL was the most sensitive to the compound compared to Candida albicans (250 µg/mL) and Candida guilliermondii (125 µg/mL).

Clioquinol derivatives as potent inhibitors of Methicillin-Resistant Staphylococcus aureus and their mechanistic study

AimsMethicillin-Resistant Staphylococcus aureus cause many nosocomial, and community-acquired infections, burdening healthcare systems globally. The aim of the current study was to identify the potent inhibitors of MRSA strains as first step towards drug discovery against MRSA related infections. Methods and ResultsClioquinol derivatives 1–10 were evaluated against MRSA strains, using microplate alamar blue assay (MABA). Among them compounds 1–3, and 6–8 were found to be active with MIC values within the range of 61.08–213.58 µM. Compounds 1, and 7 were found highly potent with MIC values of 64.04 and 61.08 µM, respectively. Both these compounds also showed non-covalent interactions with active site key residues of topoisomerase IV enzyme in molecular docking studies. Mechanisms of action of the most active compounds 1, and 7 were further studied through AFM, and fluorescence microscopy. It was observed that compounds 1, and 7 caused a massive destruction in shape, and greatly reduced the size and number of viable cells. Flow cytometry analysis showed a significant rise in DiBAC4(3) fluorescence, and a non-significant rise in PI fluorescence indicating increased bacterial membrane depolarization of treated cells. Most importantly the clioquinol derivatives 1, and 7 did not cause any hemolytic effect. Moreover, all the compounds were found to be non-cytotoxic to BJ (Human fibroblast) normal cell line. ConclusionOur findings suggest that clioquinol derivatives 1, and 7 possess highly potent antibacterial activity against three MDR, and one sensitive strains of S. aureus. Significance and impact of the studyClioquinol derivatives 1, and 7 could be further studied as potential antibacterial agents.

Grewia flava twig extracts: phytochemical, antioxidant, and antimicrobial evaluations

BackgroundGrewia flava infusions are consumed to assist with kidney problems and stomach ailments. However, there are no scientific data on the phytochemical profile or biological properties to validate its folklore use. Thus, the study aimed to assess the phytochemical profile, antioxidant, and antimicrobial activities of Grewia flava twig extracts.MethodologyThe antioxidant activities of the extracts were assayed using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, reducing power, metal chelation, and total phenolic and flavonoid content assays. The agar well diffusion and microdilution methods were used for crude extracts and fractions (from 80% methanol extract) for antimicrobial screening against P. aeruginosa, S. aureus, E. coli, B. subtilis, A. niger, and R. oryzae.ResultsThe 80% methanol twig extract (250.00 ± 2 GAE/g) exhibited a high concentration of phenolic content, followed by the distilled water extract (192.00 ± 2 mg GAE/g) and the hexane extract (43.10 ± 0.2 mg GAE/g). Fraction 14 of the methanol twig extract exhibited MIC values of 0.21–0.31 mg/mL against all test microorganisms. The root and twig extracts exhibited significant antioxidant and antimicrobial activities, which were attributed to the extracts of bioactive phytochemical compounds such as alkaloids, flavonoids, saponins, steroids, glycosides, anthraquinones, and tannins that were detected in the extracts. Also, the root and twig non-polar extracts were subjected to gas chromatography–mass spectrometry analysis, which identified several bioactive compounds like betulin, β-amyrin, palmitic acid, lupenone, and phytol, highlighting the potential of the plant species as a botanical drug.ConclusionsThe study supports the traditional use of plant roots and twigs for treating various ailments, indicating their medicinal value. The twigs can be used in place of the roots to guarantee Grewia flava harvesting that is sustainable. However, a comparison of the quantities of the active compound in the twigs and roots using LC–MS is crucial.

A versatile precursor for one‐pot synthesis of novel azo‐thiazole and thiazole scaffolds as prospective antimicrobial and antioxidant agents

AbstractIn this study, we present a simple method for preparing a new series of thiazoles with excellent isolated yields. To synthesize the target thiazole scaffolds, a straightforward one‐pot procedure was developed including an amine‐mediated reaction of isoxazolethiazolidin‐4‐one derivative, thiosemicarbazide, and appropriate hydrazonyl chlorides. The reaction conditions for this one‐pot protocol were optimized by experimenting with different solvents and amines. The best results were achieved by conducting the reaction in dioxane with triethylamine at 100°C for 5 h. The structures of the desired products were proved by different elemental analyses and spectral data. Additionally, the antimicrobial efficacy of all target derivatives was assessed against various types of microorganisms. The results observed indicated that the antimicrobial activity of the thiosemicarbazone derivative 2 was the strongest activity among the new series, with MIC values ranging from 0.03 ± 0.01 to 0.98 ± 0.15 μg/mL. Moreover, antioxidant evaluations were conducted on all the desired targets, using ascorbic acid as a reference drug. Significantly, derivatives 2 and 10 demonstrated the most promising antioxidant inhibitory effects. Additionally, further toxicity studies were performed on the most active novel compounds, revealing their best drug‐like properties and varying toxicity risks in humans.

Novel Penicillin Derivatives Against Selected Multiple-drug Resistant Bacterial Strains: Design, Synthesis, Structural Analysis, In Silico and In Vitro Studies.

The rising numbers of multiple drug-resistant (MDR) pathogens and the consequent antibacterial therapy failure that resulted in severe medical conditions push to illustrate new molecules with extended activity against the resistant strains. In this manner, chemical derivatization of known antibiotics is proposed to save efforts in drug discovery, and penicillins serve as an ideal in this regard. Seven synthesized 6-aminopenicillanic acid-imine derivatives (2a-g) were structure elucidated using FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. In silico molecular docking and ADMET studies were made. The analyzed compounds obeyed Lipinski's rule of five and showed promising in vitro bactericidal potential when assayed against E. coli, E. cloacae, P. aeruginosa, S. aureus, and A. baumannii. MDR strains using disc diffusion and microplate dilution techniques. The MIC values were 8 to 32 μg/mL with more potency than ampicillin, explained by better membrane penetration and more ligand-protein binding capacity. The 2g entity was active against E. coli. This study was designed to find new active penicillin derivatives against MDR pathogens. The products showed antibacterial activity against selected MDR species and good PHK, PHD properties, and low predicted toxicity, offering them as future candidates that require further preclinical assays.

8-Aminoquinoline derived two Schiff base platforms: Synthesis, characterization, DFT insights, corrosion inhibitor, molecular docking, and pH-dependent antibacterial study

The current research divulges the synthesis of two new Schiff base (SB) (LNAPH/LO-VAN) derived from 8-aminoquinoline (8-AMQ) in the presence of 2-hydroxy naphthaldehyde (NAPH) and ortho-vanillin (O-VAN) in CH3OH solvent. They are structurally characterized by spectroscopic methods (IR/Raman/UV–vis/DRS/NMR) and SEM-EDX. SB compounds have a biologically active avenue of azomethine/imine group (H–C=N) that can donate N e's to Mn + ions, showing coordinating flexibility. The –OH and imine (H–C=N) groups are stable in air, light, and alkalis but undergo acidic environments hydrolysis, separating –NH2 and carbonyl compounds. Moreover, buffer solutions with a pH range of 4–6 release aldehyde. Molecular electrostatic potential (MEP), Frontier molecular orbitals (FMO), Fukui function, and Non-linear optical (NLO) were conducted to elucidate SBs chemical potency, optoelectronic significance, and corrosion inhibitor. Accordingly, the calculated ΔE of FMO for LNAPH and LO-VAN is 3.82 and 4.08 eV, ensuring potent biological function. DFT supported the experimental and theoretical IR spectral correlation to enrich better structural insights. NLO-based polarizability (α) and hyperpolarizability (β) factors successfully explore the potential optoelectronic significance. Molecular docking experiments were simulated against DNA, anti-COVID-19, and E. coli. The potential microbiological activity was screened against the bacterial strains E. coli, Klebsiella, Bacillus, and Pseudomonas sp. based on zone of inhibition and MIC values. These experiments also explored the fact that LNAPH and LO-VAN discourage microbial cell biofilms and corrosion. We extensively covered the as-prepared compounds' pH-dependent bacterial effects.

Exploring the Bioactivity of Siddhalepa Asamodagam Spirit from Seeds of Trachyspermum roxburghianum (DC.) H. Wolff

Objectives The water distillate derived from Trachyspermum roxburghianum seeds has been traditionally employed in medicine for treating stomach infections and gastric ulcers. However, no systematic study has been conducted to evaluate its efficacy. Therefore, the present study focused on evaluating the potential health benefits, including the chemical constituents of the distillate. This distillate was prepared and identified as Siddhalepa Asamodagam Spirit (Sid.AS). Methods The chemical constituents of Sid.AS were identified and quantified using Gas Chromatography-Mass Spectrometry (GC-MS) method. The antioxidant potential of Sid.AS samples was assessed in vitro using DPPH and ABTS assays. Various concentrations of Sid.AS were subjected to antimicrobial, anti-obesity, anti-diabetic, anti-inflammatory, and urease inhibition assays according to the standard methods specified by the Ayurvedic Department in Sri Lanka. Results Thymol was identified as the major compound in Sid.AS through GC-MS analysis. Sid.AS demonstrated significant anti-urease, anti-inflammatory, anti-lipase, and antioxidant activities, as evidenced by low IC50 values compared to the positive controls. This suggests its potential in controlling gastric-related disorders, scavenging free radicals, and managing obesity by inhibiting the breakdown and absorption of fats. Additionally, Sid.AS exhibited inhibitory effects against alpha-amylase and alpha-glucosidase enzymes, indicating potential anti-diabetic activity by regulating blood sugar levels. Sid.AS displayed strong antimicrobial activity against tested microorganisms, with higher zones of inhibition and lower MIC and MLC values, indicating its effectiveness in combating microbial infections. Findings from the anti-lipase assay demonstrated activity comparable to that of the positive control, Orlistat. Conclusion The findings of Sid.AS suggest its potential as a multi-functional bioactive herbal distillate with various pharmacological activities. Our results highlight that Sid.AS is a promising natural herbal extract with diverse pharmacological properties, including anti-urease, antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, and antimicrobial activities. Further research and development could explore its potential applications in various therapeutic areas.

GC-MS-MS analysis and biological properties determination of Mentha piperita L., essential oils

This research explores the therapeutic properties and medicinal potential of Mentha piperita L. (M. piperita) essential oil (EO) (MPEO) harvested in the province of Ouezzane, northwestern Morocco. We conducted a comprehensive chemical composition analysis of MPEO using gas chromatography-mass spectrometry (GC-MS) to identify its major components. The predominant constituents were pulegone (17.56%), mintlactone (10.62%), D-carvone (9.24%), eucalyptol (7.53%), and thymol (6.06%). The antidiabetic effects were assessed by measuring the inhibition of two digestive enzymes (α-glucosidase and α-amylase). The dermatoprotective effect was evaluated based on the inhibition of elastase and tyrosinase, and neuroprotective activity was studied by examining the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Additionally, molecular docking analysis was used to determine the interactions between the main MPEO compounds and the enzymes targeted. Antioxidant activity was estimated using in vitro FRAP, DPPH, and ABTS assays. Furthermore, the antibacterial potential was evaluated against pathogenic strains using the micro-broth dilution method. Our results indicate significant antioxidant and neuroprotective activities of MPEO, along with promising antidiabetic and dermatoprotective potential, surpassing references. Additionally, all bacterial strains tested were susceptible to MPEO, with MIC values lower than those of MBC for all bacteria except L. monocytogenes. These in vitro findings were supported by in silico analysis, showing that menthelactone and pulegone presented strong binding affinities with key enzymes involved in glucose regulation and pigmentation. MPEO, rich in bioactive compounds, has shown promising potential. The main components of this oil offer innovative prospects for the development of drugs and natural therapeutic applications.

Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties.

There is a critical need for the discovery of novel and effective antibacterial or anticancer molecules. Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%. Their molecular structures were successfully confirmed using different spectroscopic methods including 1H/13C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method. Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 μg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC50 value of 43.64 g/mL. The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required.

Antimicrobial and anticancer activities of diazenyl compounds

Three heterocyclic diazenyl compounds were synthesized by diazotization of 3-aminopyridine and aniline, followed by coupling with 8-aminoquinoleine, morpholine, 1,2,3,4-tetrahydroquinoleine, respectively. The obtained azo compounds are brown to yellow in color and were characterized by various methods such as NMR and X-rays. The synthesized compounds were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. The MIC of the tested compounds, determined by the microdilution method, showed potential antimicrobial activity against all tested microorganisms. 1-(3-pyridyl)-2-(morpholin-4-yl)diazene (8) and 1-(3-pyridyl)-2-(tetrahydroquinolin-1-yl)diazene (10) showed strong activities against C. albicans with MIC values of 150 µM and 120 µM respectively. 1-(4-trifluoromethylphenyl)-2-(8-aminoquinolin-5-yl)diazene (4) showed the broadest spectrum of activity with good MICs of 1380–2760 µM on the four strains. These diazenyl compounds were also screened for their anticancer activity against breast (MCF-7), lung (Calu-3), pancreas (PANC-1) and prostate (PC-3) cancer cells and on normal fibroblasts. The results showed good anticancer activities on tumor lines with IC50 values ranging from 9.4 to 98 µM. The best anticancer activity was obtained with compound 4 on Calu-3 cancer cells with an IC50 of 9.4 µM. The results suggest that compound 4 is an interesting scaffold for pharmacomodulation as suggested by ADME study.

Antimicrobial Metabolites from the Freshwater Fungus Tubeufia longihelicospora Strain GZCC 23-0405

In this study, five metabolites were successfully isolated from the culture medium of Tubeufia longihelicospora strain GZCC 23-0405, comprising two dimeric naphtha-γ-pyrones (1–2), two dimeric coumarins (3–4), and one alkaloid (5). The elucidation of their chemical structures relied on a combination of NMR, MS, and optical rotation methods. Interestingly, these compounds represent the first instances of such metabolites being isolated from helicosporous hyphomycetes. Additionally, compounds (1) and (2) exhibited significant antimicrobial potential, with MIC and MBC values of 62.0 μg mL-1 and 248 μg mL-1, respectively, against Pseudomonas aeruginosa. This study provides a comprehensive account of the extraction, isolation, structural characterization, and antimicrobial properties of these compounds, shedding light on their potential significance in the field of natural product research.

Phytochemical Analyses and Antibacterial Activities of Jatropha tanjorensis J. L. Ellis and Saroja Leaves Extract against Clinical Pathogens

Aim: The aim of this study was to investigate the phytochemical and antimicrobial characteristics of leaf extracts from Jatropha tanjorensis plant against some selected clinical pathogens. Study Design: Experimental Study design (Quantitative). Place and Duration of Study: Sample: The bacteria were obtained from the stock culture of the Microbiology laboratory at LUTH, Idi-Araba, Lagos State and Department of Biological Sciences, Bells University of Technology, Ota, Ogun State. Methods: Fresh Jatropha tanjorensis leaves were obtained, identified, and then finely ground after being dried at room temperature. To obtain the extracts, two hundred grams (200g) of the leaves were macerated in one thousand milliliters (1000ml) of solvent. Phytochemical analyses were done on the extract utilizing suitable standard protocols. Using the agar well diffusion method, the leaf extracts' antibiotic sensitivity was assessed against selected bacteria, including Salmonella typhi, Pseudomonas aeruginosa, Bacillus subtilis ATCC 6633, Enterococcus faecalis FELAO97, Escherichia coli, Bacillus aureus ATCC 25923, and Bacillus aureus ATCC 25923. Results: The qualitative phytochemical analysis revealed that while phlobatannins were absent from all extracts, other compounds found included saponin, alkaloids, phenols, flavonoids, reducing sugars, terpenoids, steroids, and tannins. According to the quantitative phytochemical analysis, reducing sugars from methanolic extract had the lowest concentration (20.39 mg/100g) and flavonoids from hot water extract had the highest concentration (98.55 mg/100g). With a zone of inhibition of 19.83 mm against S. aureus, the cold-water extract exhibited the highest inhibitory effect, while the methanolic extract displayed the lowest zone of inhibition, 13.17 mm, against B. subtilis. When compared to other isolates, B. subtilis had the lowest MIC value of 10.24 mg/ml and other isolates had the highest MIC value of 20.48 mg/ml. A GC-MS analysis identified fifty-seven (57) bioactive compounds with 1, 2, 3-Benzenetriol having the highest percentage of 66.38%. Conclusion: This study suggests that Jatropha tanjorensis may be a potential antibacterial drug, but more thorough study and collaboration are still necessary.

Synthesis and computational studies of new pyridine, pyrazole, pyran, and pyranopyrimidine-based derivatives of potential antimicrobial activity as DNA gyrase and topoisomerase IV inhibitors

In this study, new derivatives based on pyridine, pyrazole, pyran, and pyranopyrimidine scaffolds 5–14 were designed and synthesized. The newly synthesized compounds were characterized using microanalytical and spectral data. Using amoxicillin and amphotericin B, two common antibacterial and antifungal medications, respectively, the antimicrobial activity of the new compounds was assessed against a variety of strains of both Gram-positive and Gram-negative bacteria as well as fungal infections. The most promising activity was achieved by pyridine-based derivatives 5, 7a, and 7b, which exhibited MIC values ranging from 0.95 to 18.04 µM against the examined bacterial strains and ranging from 4.65 to 33.16 µM against the examined fungal strains. The later derivatives were also evaluated as E. coli DNA gyrase B/topoisomerase IV inhibitors in comparison with novobiocin as a standard drug. Although the assessed candidates 5, 7a, and 7b exhibited a promising suppression impact against E. coli DNA gyrase B (IC50 = 3.11 ± 0.14, 3.85 ± 0.20, and 4.05 ± 0.10, respectively, IC50 novobiocin= 3.64 ± 0.10 µM), they showed detectable less suppression impact against Topoisomerase IV than that of the reference drug with IC50 values of 19.72 ± 1.00, 79.33 ± 0.25, 85.14 ± 0.10, and 13.42 ± 0.05 µM, respectively. Additionally, the safety profiles of 5, 7a, and 7b against WI38 cells were significantly superior to that of novobiocin (IC50 = 138 ± 0.33, 170 ± 0.40, 163.3 ± 0.17, and 86.2 ± 0.03 µM, respectively).Lastly, molecular docking was used to examine the most active derivatives 5, 7a, and 7b's binding capacity to the target DNA gyrase B/topoisomerase IV. The molecules exhibited various H-interactions with the amino acid residues Asp73, Arg76, and Val71 in E. coli DNA gyrase, where compound 5 exhibited H-bonding with the Asp1069 side chain of E. coli Topoisomerase IV. Additional in silico ADMET studies were conducted to represent their oral bioavailability and drug-likeness characteristics.

Innovative ultrasonic emulsification of cinnamon essential oil pickering emulsion stabilized by rice straw-derived cellulose nanocrystals

For the first time, ultrasonic emulsification was studied for cinnamon essential oil (CEO) Pickering emulsion, stabilized by cellulose nanocrystal (CNC) from rice straw. Sonication proved to be an effective method for emulsifying CEO, creating small emulsion droplets around 700 nm in size, with an even dispersion characterized through a low polydispersity index. The biomass-derived CNC exhibits high encapsulation efficiency (> 95 %) with varying CEO concentration (5–25 vol%), creating droplets with negative surface charge with limited aggregation of emulsions. Optimization through the Box Behnken design using response surface methodology provides a model for the interaction and effects of variables towards the formulation. Optimal condition was concluded to be at 11.47 vol% CEO, 0.84 wt/vol% CNC and at 6 sonication cycles. The optimized Pickering emulsions retain the antimicrobial properties of CEO, with a large inhibition zone and low MIC value of around 0.048 vol% CEO. DPPH inhibition assay indicates that the emulsification process enhances the antioxidation properties of cinnamon essential oil, expressed through a lower IC50 of 0.90 vol% CEO, in comparison to pure essential oil at 1.33 vol% CEO. Overall, this research proposes a novel approach towards using nanocellulose as carriers for essential oil with potential in a large variety of applications.

Assessment of pharmacokinetics-pharmacodynamics to support omadacycline dosing regimens for the treatment of patients with acute bacterial skin and skin structure infections.

Pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy were evaluated using data from omadacycline-treated patients with acute bacterial skin and skin structure infections (ABSSSI) enrolled in two phase 3 studies. Patients received omadacycline 100 mg intravenously (IV) every 12 hours for two doses, followed by 100 mg IV every 24 hours (q24h), with the option to switch to 300 mg oral (PO) q24h after 3 days or 450 mg PO q24h for two doses, followed by 300 mg PO q24h for a total duration of 7-14 days. Clinical response was evaluated at 48-72 hours [early clinical response (ECR)], end of treatment (EOT), and 7-14 days after EOT. Using a population pharmacokinetic (PK) model and PK data from patients with Staphylococcus aureus at baseline, omadacycline free-drug plasma area under the concentration-time curve (AUC) values were determined, and the relationships between free-drug plasma AUC:MIC ratio and dichotomous efficacy endpoints were evaluated. Using these relationships, the population PK model, simulation, and an omadacycline MIC distribution for S. aureus, mean percent probabilities of response were evaluated. Statistically significant PK--PD relationships were identified for ECR (P = 0.016 and 0.013 for optimized two- and three-group free-drug plasma AUC:MIC ratios, respectively). At an MIC value of 0.5 µg/mL, percent probabilities of model-predicted success for ECR based on the univariable PK-PD relationships using continuous and two-group free-drug plasma AUC:MIC ratio variables were 91.9 and 95.6%, respectively, for the IV-to-PO dosing regimen and 89.3 and 88.4%, respectively, for the PO-only dosing regimen. These data support for omadacycline IV-to-PO and PO-only dosing regimens for ABSSSI and an omadacycline susceptibility breakpoint of 0.5 µg/mL for S. aureus.

Enhancing bioactivity of Callistemon citrinus (Curtis) essential oil through novel nanoemulsion formulation

The main focus of this study was to create a stable and efficient nanoemulsion (NE) using Callistemon citrinus essential oil (EO). Various factors affecting the NE’s stability were optimized including oil %, Tween 80%, time of sonication, and its accelerated stability was examined. The research also considered the antibacterial, antifungal, and larvicidal effects of the optimized NE (B10). The optimum NE stood out for its stability, featuring a particle size of 33.15 ± 0.32 nm. Analysis via IR spectroscopy confirmed successful EO encapsulation in B10. The formulation remained stable for six months, with B10 showing significantly higher antibacterial and antifungal potency compared to the pure oil. When samples were subjected to tests against Fusarium oxysporum, B10 exhibited a MIC value of 62.5 mg/mL, whereas the pure oil showed a MIC value of 250 mg/mL. This indicates that the B10 formulation was 50 times more effective than the EO. In terms of antibacterial activity against Escherichia coli, the MIC value was 0.256 mg/mL for B10 and 4 mg/mL for the EO. Also, pure oil and B10 displayed larvicidal effects against Chilo suppressalis (Walker) larvae, with B10 eliminating 95.2% of larvae in 48 h. Overall, stable and optimum C. citrinus NE with its strong antimicrobial qualities, shows promise as an effective fungicide and insecticide.

In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol

Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.

Taxonomic characterization and secondary metabolite production of newly isolated Streptomyces sp. MC12

An actinobacterium newly isolated from soil during a screening study was identified as Streptomyces sp. MC12 (GenBank accession number: PP757795) based on 16S rRNA analysis. For secondary metabolite production, fermentation was carried out in ISP 2 broth at 30°C, pH 7.3, for seven days under shaking conditions at 180 rpm. As a result of fermentation studies, the antagonistic effect of the crude extract, obtained through ethyl acetate extraction, against various microorganisms was determined. The MIC values of the extract against Staphylococcus aureus and Escherichia coli were 101.3 µg/mL and 153.6 µg/mL, respectively. It was also found to exhibit strong antifungal activity against Penicillium spp. Streptomyces sp. MC12, which displays both antifungal and antibacterial properties, is considered a potential secondary metabolite producer for future studies, particularly in pharmacology and the biocontrol of fungal pathogens.

Synergistic Interactions between Selected β-Lactam Antibiotics and Cinnamic Acid and Its Chosen Derivatives.

Staphylococcus epidermidis, a component of human microbiota, may also cause life-threatening opportunistic infections. These are becoming increasingly common infections associated with the implantation of various implants. Due to the exhaustion of antibiotic resources, new substances with antimicrobial activity are being sought. The present study examined the antibacterial effect of cinnamic acid and its derivatives and their combinations with β-lactam antibiotics on the growth of Staphylococcus epidermidis strains isolated from vascular infections. The data obtained during the research indicated that cinnamic acid and its derivatives, sinapic acid, ferulic acid, and p-coumaric acid, have weak antibacterial activity (MIC values at the level of 2048 and 4096 mg/L). The combination of cinnamic acid and its derivatives with β-lactam antibiotics increases the effectiveness of their action and may demonstrate various pharmacological effects depending on the established cutoff.