Antibiotic Properties Research Articles

Targeting the G-quadruplex as a novel strategy for developing antibiotics against hypervirulent drug-resistant Staphylococcus aureus

BackgroundThe rapid emergence of multiple drug-resistant (MDR) bacterial pathogens and the lack of a novel antibiotic pipeline pose a serious threat to global healthcare. The limited number of established targets further restricts the identification of novel antibiotics to treat life-threatening MDR infections caused by Staphylococcus aureus strains. Therefore, novel targets for developing antibiotics are urgently required. In this study, we hypothesized that the G-quadruplex (G4)-binding ligands can be used as novel antibiotics as their binding can possibly downregulate/block the expression of vital genes.MethodsTo test this, first we screened the antibiotic properties of representative G4-binding ligands against hypervirulent and MDR S. aureus USA300 and determined the in vitro and in vivo antibacterial activity; and proposed the mechanism of action by applying various microbiological, infection, microscopic, and biophysicochemical techniques.ResultsHerein, among screened G4-binding ligands, N-methyl mesoporphyrin IX (NMM) showed the highest antibacterial activity against S. aureus USA300. NMM exhibited a minimum inhibitory concentration (MIC) of 5 μM against S. aureus USA300, impacting cell division and the cell wall by repressing the expressions of genes in the division cell wall (dcw) gene cluster. Genome-wide bioinformatics analysis of G4 motifs and their mapping on S. aureus genome, identified the presence of G4-motif in the promoter of mraZ, a conserved master regulator of the dcw cluster regulating the coordinated cell division and cell wall synthesis. Physicochemical assessments using UV–visible, circular dichroism, and nuclear magnetic resonance spectroscopy confirmed that the G4-motif present in the mraZ promoter formed an intramolecular parallel G4 structure, interacting with NMM. In vivo reporter followed by coupled in vitro transcription/translation (IVT) assays confirmed the role of mraZ G4 as a target interacting NMM to impose extreme antibacterial activity against both the gram-positive and -negative bacteria. In-cell and in vivo validation of NMM using RAW264.7 cells and Galleria mellonella; respectively, demonstrated that NMM exhibited superior antibiotic activity compared to well-established antibiotics, with no observed cytotoxicity.ConclusionsIn summary, the current study identified NMM as a broad-spectrum potent antibacterial agent and elucidated its plausible mechanism of action primarily by targeting G4-motif in the mraZ promoter of the dcw gene cluster.

Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development

MtbClpC1 is a promising drug target against tuberculosis. Recent studies have shown that several natural product antibiotics targeting the unfoldase N-terminal domain can impair MtbClpC1 function resulting in cell death. While the pharmacological properties of these natural product antibiotics prevent their use in the clinic, similar molecules binding to the same binding pockets can result in new drugs against Mtb. Here we demonstrate that we successfully used in silico screening to identify new ClpC1 N-terminal domain binders with micromolar affinity from a small compound library. In addition, we experimentally demonstrate that the new compounds bind to the same pockets used by the natural product antibiotics and inhibit ClpC1 function.

Unlocking nature's pharmacy: Euphorbia hirta (L.) as a potent defense against Escherichia coli and Klebsiella pneumoniae infections in Tanzania

BackgroundUrinary tract infections (UTIs) are among the most common bacterial infections, primarily caused by Escherichia coli and Klebsiella pneumoniae, both of which have mostly developed resistance to various antibiotics. The Maasai and Meru communities in Tanzania have traditionally used Euphorbia hirta to combat resistant pathogens, particularly those causing UTIs. PurposeThis study aimed to evaluate the antimicrobial compounds of aqueous extracts and the antibacterial compounds in methanolic extracts of E. hirta. We specifically focused on the antibacterial activity of aqueous and methanolic extracts against E. coli and K. pneumoniae strains, which are significant contributors to UTIs. Study designIn March 2024, we randomly collected E. hirta plant parts from the Kikwe and Kisongo wards in the Arusha region of Tanzania. The samples were washed with distilled water and shade-dried for three weeks to prevent the degradation of bioactive compounds. After drying, the samples were powdered using a laboratory grinder and stored in sterile nylon bags. MethodsWe conducted qualitative and quantitative analyses to assess the presence of various phytochemicals, including alkaloids, saponins, coumarins, terpenoids, quinones, flavonoids, and glycosides, in the aqueous and methanolic extracts of E. hirta. To identify specific phytochemical compounds in these extracts, we used gas chromatography-mass spectrometry (GC–MS) and disc diffusion assays to test their antibacterial activity against E. coli and K. pneumoniae. ResultsThe GC–MS analysis identified sixteen potential bioactive compounds with antibiotic properties, including dodecanal, trans-Farnesol, phytol, 13-tetradecynoic acid, methyl ester, cis-5,8,11,14,17-Eicosapentaenoic acid, 2(4H)-Benzofuranone, 5,6,7,7a-tetrahydro-4,4,7a-trimethyl-, (R)-, paromomycin, decanoic acid, methyl ester, azelaic acid, undecanoic acid, 10-methyl-, methyl ester, palmitoleic acid, 9,12,15-Octadecatrienoic acid (Z,Z,Z), 7-Hydroxy-3-(1,1-dimethylprop-2-enyl) coumarins, linoleyl methyl ketone, and 8,11,14-Eicosatrienoic acid, methyl ester (Z,Z,Z). When tested at a concentration of 1 g/mL, all extracts demonstrated significant antibacterial activity. The methanolic extract exhibited the highest performance, with a minimum inhibition zone of 12.0 ± 2.35 mm, followed by the aqueous cold extract at 9.25 ± 1.75 mm, and the aqueous boiled extract at 8.0 ± 1.35 mm. ConclusionThe traditional methods employed by the Maasai and Meru communities for preparing herbal medicine from E. hirta, such as boiling and soaking in cold water, seemed to be effective in treating UTIs. Organic solvent extraction using methanol generally showed superior antibacterial activity compared to aqueous extraction. However, soaking in cold water produced extracts with higher inhibitory activity against E. coli, while boiling was more effective against K. pneumoniae. This study validates the local practices of E. hirta preparation, suggesting that water-based extracts could be both effective and safe for treating certain bacterial strains responsible for UTIs in the Arusha region.

Aging-mediated selective adsorption of antibiotics by tire wear particles: Hydrophobic and electrostatic interactions effects.

Tire wear particles (TWPs), as a prevalent form of microplastic pollution in aquatic environments, have been shown to adsorb antibiotics, potentially exacerbating their toxic effects. This study provides a comprehensive analysis of the adsorption of ofloxacin (OFL), ciprofloxacin (CIP), sulfadiazine (SDZ), and tetracycline (TC) on TWPs that have undergone various aging processes, including cyclic freeze-thaw and ozone aging. We observed a significant increase in the specific surface area (SBET) of TWPs after aging, from an initial 2.81±0.29 to 6.63±0.16m2/g for ozone-aged TWPs. This enhancement in surface area and pore volume led to a respective 1.36-fold and 28-fold increase in adsorption capacity for OFL and CIP, highlighting the substantial impact of aging on TWPs' adsorptive properties. Conversely, the adsorption of SDZ and TC was reduced post-aging, suggesting a complex interaction between antibiotic physicochemical properties and TWPs' surface characteristics. The pseudo-second-order model, indicating chemisorption interactions, effectively described the adsorption kinetics, with the Freundlich isotherm model capturing the adsorption behavior more accurately than the Langmuir model. Our findings underscore the critical role of hydrophobic and electrostatic interactions in the adsorption process, particularly for SDZ and TC. This study's results offer crucial insights into the environmental implications of TWPs, emphasizing the need for further research on their role in the transport and fate of antibiotics in aquatic ecosystems.

Investigating Potential Anti-Bacterial Natural Products Based on Ayurvedic Formulae Using Supervised Network Analysis and Machine Learning Approaches

Objectives: This study implements a multi-dimensional methodology to systematically identify potential natural antibiotics derived from the medicinal plants utilized in Ayurvedic practices. Methods: Two primary analytical techniques are employed to explore the antibiotic potential of the medicinal plants. The initial approach utilizes a supervised network analysis, which involves the application of distance measurement algorithms to scrutinize the interconnectivity and relational patterns within the network derived from Ayurvedic formulae. Results: 39 candidate plants with potential natural antibiotic properties were identified. The second approach leverages advanced machine learning techniques, particularly focusing on feature extraction and pattern recognition. This approach yielded a list of 32 plants exhibiting characteristics indicative of natural antibiotics. A key finding of this research is the identification of 17 plants that were consistently recognized by both analytical methods. These plants are well-documented in existing literature for their antibacterial properties, either directly or through their bioactive compounds, which suggests a strong validation of the study’s methodology. By synergizing network analysis with machine learning, this study provides a rigorous and multi-faceted examination of Ayurvedic medicinal plants, significantly contributing to the identification of natural antibiotic candidates. Conclusions: This research not only reinforces the potential of traditional medicine as a source for new therapeutics but also demonstrates the effectiveness of combining classical and contemporary analytical techniques to explore complex biological datasets.

Synthesis, characterization and biological profile of some new dihydropyrimidinone derivaties.

The rise of drug-resistant bacteria, viruses, and fungi has prompted the search for new drugs without cross-resistance to current treatments. As a result, the aim of this research was to synthesize various types of dihydropyrimidinones heterocyclic compounds and screened them for their antibiotic properties. Newly synthesized dihydropyrimidinone derivatives were characterized spectroscopically using proton NMR (1HNMR), and FT-IR. These substances were then subjected to molecular docking studies via Auto dock Vina software to determine their affinity for binding to proteins from different bacterial strains including (Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), Mycobacterium luteus (M. luteus), Salmonella typhi (S.typhi), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli) and fungal (Candida glabrata (C. glabrata), Candida albicans (C. albicans), and Saccharomyces cerevisiae (S. cerevisiae) strains. Also in-vitro anti-fungal, anti-bacterial and anti-oxidant activity was performed by using ager well diffusion method and DPPH assay respectively. Moreover, the In-vivo biological evaluation of these derivatives was conducted by using carrageenan-induced hind paw model. The cytotoxicity profile of the synthesized derivatives was done via in-vitro MTT assay. All newly synthesized derivatives were confirmed via the multiple spectroscopic analysis techniques. All derivatives showed good binding affinities against the multiple targeted protein with. Compound 4c exhibited hightest potential with -10kcal/mol against bacterial strains. 4b showed best antifungal potential with -10.8kcal/mol binding affinities. For Bacillus subtilis compound 4b and 4c performed best with 17mm±2.21. for anti-fungal activity against Candida glabrata, amongst the five newly formed compounds, 4a showed best activity with 19mm±1.22 The analogue 4b exhibited best anti-oxidant potential with 63.85±1.39. Compound 4a and 4b showed highest anti-inflammatory potential with 1.011mm±0.247mg/kg and 1.447±0.212mg/kg in countering inflammation by targeting toll-like receptor activation and reduce the inflammation in hind paw edema. The selected derivatives exhibited no toxicity profile with 99 % and 98 % cell survival rate using compound 4a and 4b. Research has been done on the multiple biological activities of dihydropyrimidinones derivatives but the innovation on MDR is still pending. New dihydropyrimidinone derivatives were developed as agents to combat drug resistance. The results of these studies showed that newly synthesized dihydropyrimidinone derivatives are remarkably effective not only as anti-biotic agents but also counter inflammation caused by carrageenan resulting from the activation of the Toll-like receptors (TLRs) signaling pathway along with the non-toxic effect. So it is concluded that the recently synthesized new dihyropyrimidinone derivatives are highly effective antimicrobial derivatives with non-toxic effects on human cell lines.

A novel nano-emulsion cream of casein isolated from raw milk for thermal and acid burn wounds

Abstract Traditionally, raw cow milk has been employed to treat acid and thermal burns due to its antibacterial, antibiotic, and antifungal properties. It also aids in preventing scarring and alleviating burn-related skin discomfort. This study focuses on evaluating a nanoemulsion cream made from casein extracted from raw cow milk for managing acid and thermal burns. Casein was isolated and used to create 2%, 5%, and 10% w/w nanoemulsion creams. Wistar albino rats were used to induce acid and thermal burns, and the healing progress was monitored by measuring wound contraction and epithelialization period. The results demonstrated significant wound healing effects of the casein creams (p<0.001) in acid burns, with the 10% w/w cream showing the highest epithelization rate in thermal burns. Raw milk also exhibited notable healing properties in acid burns. However, its effectiveness was relatively lower in thermal burns. This study suggests that raw milk and its casein-derived creams could be utilized as first-aid treatments for acid burns, though they may be less effective for thermal burns.

Analysis of the metabolite profile of mistletoe leaves (Dendrophthoe pentandra (L.) Miq.) as an Epiphyte on Lime Using the GC-MS Method

Dendrophthoe pentandra (L.) Miq., a mistletoe species from the Loranthaceae family, can thrive as an epiphyte on various host plants, including lime trees. This mistletoe has potential as a herbal plant due to its bioactive properties, stemming from a diverse range of metabolites. Therefore, this analysis aims to identify different compounds and explore groups of compounds that may exhibit potential bioactivity in ethanolic extracts of D. pentandra leaves on lime, utilizing the GC-MS method. The analysis revealed a total of 68 detected metabolite compounds, comprising 51 main compounds that represent 90.49% of the total abundance. Notably, 16 dominant compounds were identified, including Melezitose (6.64%), 3-Methylmannoside (6.38%), ß-D-Mannofuranoside, methylated (4.76%), 3-O-Methyl-D-glucose (3.70%), Myo-Inositol, 4-C-methyl (31.29%), and Tetradecanoic acid, ethyl ester (3.81%). In terms of abundance based on compound class, carbohydrates account for 65%, fatty acids for 15%, and phenols for 10%, with the remaining compounds comprising other classes. The unique compounds found in mistletoe leaves on lime exhibit various bioactivities, such as antioxidant, anticancer, antibiotic, antiseptic, antihyperglycemic, antihistamine, antiandrogenic, antiarrhythmic, antiasthmatic, and diuretic properties. Further research is necessary to explore the bioactive compounds in mistletoe D. pentandra across various potential host plants and to conduct additional metabolomic analyses.

Polymerizable Cholinium-Based Antibiotics for Polymer Carriers: Systems with Combined Load of Cloxacillin and Ampicillin.

Single and dual-drug delivery systems (DDSs) based on linear choline polymers were designed through the controlled polymerization of a pharmaceutically functionalized monomer, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium, with counterions of cloxacillin (TMAMA/CLX), or its copolymerization with [2-(methacryloyloxy)ethyl]trimethylammonium with ampicillin (TMAMA/AMP), providing antibiotic properties. This strategy was effective in attaining well-defined linear copolymers with 38-93 mol. % of TMAMA content, which were regulated by the initial ratio of TMAMA to methyl methacrylate comonomer. The polymer compositions were controlled by the total monomer conversion (40-75%), resulting in a variable degree of polymerization (DPn = 160-300) and pharmaceutical anion contents (CLX- 51-80% and AMP- 78-87%). In aqueous solution, the polymers formed particles with sizes ranging between 274 and 380 nm for CLX- systems and 288-348 nm for CLX-/AMP- systems. In vitro drug release, driven by the exchange of pharmaceutical anions with phosphate ions in phosphate-buffered saline (PBS), imitating a physiological fluid, demonstrated release efficiencies of 58-76% for CLX- (10.5-13.6 µg/mL) in single systems, and 91-100% for CLX- (12.9-15.1 µg/mL) and 97-100% for AMP- (21.1-23.3 µg/mL) in dual systems. Compared to conventional systems delivering antibiotics without a polymer carrier, the choline-based polymer DDS attained satisfactory levels of drug loading content and (co-)release from the polymer carriers, offering a promising alternative for antibiotic delivery.

PHARMACOLOGICAL AND THERAPEUTIC USE OF COLEUS AROMATICUS -A REVIEW

Coleus aromaticus Benth., (Fam. Lamiaceae), syn. Coleus amboinicus Lour. Spreng or Plectranthus ambonicus Lour, is commonly known as Indian/ country borage and ‘Pathorchur’ in Hindi and Bengali. It is listed as one of the sources of Pashanabheda in the Indian medical system. It is a big, fragrant, succulent perennial herb that is tomentose and shrubby below. It can be found in the Moluccas, Ceylon, and India. The plant's bitter, caustic leaves have been utilised for various purposes for a long time. The plant has been thoroughly studied, with many chemical compounds extracted and various biological properties demonstrated. The wide range of plants' antibacterial, anticancer, antioxidant, and natural antibiotic properties is effective. The plant is grown in gardens and is found all over India. Malaria, hepatopathy, renal and vesical calculi, cough, chronic asthma, hiccough, bronchitis, helminthiasis, colic, convulsions, and epilepsy are treated with this traditional medicinal herb. This review aims to gather all available data regarding its nutritional value, pharmacology and medicinal applications.

Biofilm formation, slime production, and antibiotic susceptibility properties of the Bacillus cereus group isolated from fresh vegetables in the Republic of Korea

Biofilm formation, slime production, and antibiotic susceptibility properties of the Bacillus cereus group isolated from fresh vegetables in the Republic of Korea

Tailored culture strategies to promote antimicrobial secondary metabolite production in Diaporthe caliensis: a metabolomic approach

BackgroundIn the search for new antimicrobial secondary metabolites of fungi, optimizing culture conditions remains a critical challenge, as standard laboratory approaches often result in low yields. While non-selective methods, such as modifying culture media, have been effective in expanding the chemical diversity of fungal metabolites, they have not yet established a direct link to key process parameters crucial for further optimization. This study investigates the capacity of Diaporthe caliensis as a biofactory for biologically active secondary metabolites, employing tailored culture media to explore the relationship between chemical diversity and critical process variables.ResultsThe metabolomic profiles, antibacterial activities, and production yields of the extracts were analyzed to progressively adjust the culture conditions. This study was conducted in five steps, evaluating carbon and nitrogen source concentration, nitrogen source type, salt supplementation, and pH adjustment. Altering the rice starch concentration affected biomass yield per unit of oxygen consumed, while modifications to the nitrogen source concentration influenced both the bioactivity and chemical space by Diaporthe caliensis. Despite changes at the metabolome level, the extracts consistently exhibited potent antibacterial activities, influenced by the nitrogen source, added salts and pH adjustments. For instance, when using corn steep liquor and rice starch, supplemented with micronutrients, different metabolites were produced depending on whether buffer or water was used, though both conditions showed similar antibacterial activities (IC50 ≈ 0.10 mg mL− 1 against Staphylococcus aureus and ≈ 0.14 mg mL− 1 against Escherichia coli). In the treatment where buffer was used to stabilize pH change, there was an increase in the production of phomol-like compounds which are associated with known antibiotic properties. In contrast, in the treatments using water, the drop in pH stimulated the production of previously unidentified metabolites with potential antimicrobial activity.ConclusionsThis study proposes a strategic methodology for the tailored formulation of culture media aiming to promote the biosynthesis of diverse secondary metabolites. This approach revealed the critical role of nutrient limitation and pH regulation in stimulating the production of polyketide-lactone derivatives, including the antibiotic phomol. Ultimately, the systematic, custom-designed culture conditions developed in this work offer a promising strategy for expanding the chemical diversity of Diaporthe caliensis, while providing valuable insights into the key parameters needed for optimizing this fungal biofactory.Graphical

Structural Antibiotic-Coated Hindfoot Nail Preparation: A Technique Guide

The current guide describes a technique that has been in place at the University of Louisville for several years and has been utilized to create structural antibiotic hindfoot nails. This has the intention of creating a stable construct that can be utilized in the setting of previous osteomyelitis, or that is at high risk of developing infections in the postoperative state. This technique guide provides a reproducible way to apply an antibiotic delivery system to a tibiotalocalcaneal nail at the time of definitive surgical intervention. It described our method at rural state level one trauma hospital of utilizing antibiotic-impregnated polymethylmethacrylate around a nail for both antibiotic properties as well as structural properties. Antibiotic delivery systems are a well-researched surgical tool, combining this with a hindfoot nail offers definitive surgical management of otherwise complicated surgical cases. Although this technique has been in use at the University of Louisville for many years, additional research should be done to determine long-term outcomes. Level of Evidence: Diagnostic Level VII. See Instructions for Authors for a complete description of levels of evidence.

Investigating the efficacy of dapsone in treating sepsis induced by cecal ligation and puncture surgery in male mice.

Sepsis is a life-threatening condition caused by the body's response to an infection. Dapsone is a sulfone with antibiotic properties, and experimental evidence suggests it has significant anti-inflammatory and anti-oxidative stress effects. The objective of this study was to investigate the efficacy of dapsone in mice after CLP (cecal ligation and puncture) surgery, which is a model for inducing sepsis. The study divided animals into five groups: CLP, sham, and three groups receiving different doses of dapsone (0.5, 1, 2mg/kg). Sepsis was induced through CLP surgery, followed by dapsone administration. In each group, half of the mice were used to evaluate levels of various markers and pathological changes at 24h post-CLP, while the other half was used to record the mortality rates within 96h. The results showed that single-dose administration of dapsone at (0.5, 1, 2mg/kg) after CLP surgery improved survival compared to the CLP group. Dapsone was also associated with a significant reduction in pro-inflammatory cytokines TNF-α, IL-1β, IL-6, NO, and MPO, as well as lactate and creatinine serum levels. However, dapsone did not have a significant effect on urea serum levels. In conclusion, the data suggest that dapsone treatment leads to increased survival in septic mice after CLP, and due to its ability to reduce TNF-α, IL-1β, IL-6, MPO,and lactate levels, it has anti-inflammatory effects in sepsis. The sepsis treatment with dapsone in mice protects against inflammation and oxidative stress.

A Comprehensive Review on Niosomes as a Strategy in Targeted Drug Delivery: Pharmaceutical, and Herbal Cosmetic Applications.

Niosomes are newly developed, self-assembling sac-like transporters that deliver medication at a specific site in a focused manner, increasing availability in the body and prolonging healing effects. Niosome discovery has increased drugs' therapeutic effectiveness while also reducing adverse effects. This article aims to concentrate on the increase in the worldwide utilization of niosomal formulation. This overview presents a thorough perspective of niosomal investigation up until now, encompassing categories and production techniques, their significance in pharmaceutical transportation, and cosmetic use. The thorough literature review revealed that extensive attention has been given to developing nanocarriers for drug delivery as they hold immense endeavor to attain targeted delivery to the affected area simultaneously shielding the adjacent healthy tissue. Many reviews and research papers have been published that demonstrate the interest of scientists in niosomes. Phytoconstituents, which possess antioxidant, antibiotic, anti-inflammatory, wound healing, anti-acne, and skin whitening properties, are also encapsulated into niosome. Their flexibility allows for the incorporation of various therapeutic agents, including small molecules, proteins, and peptides making them adaptable for different types of drugs. Niosomes can be modified with ligands, enhancing their targeting capabilities. A flexible drug delivery mechanism provided by non-ionic vesicles, which are self-assembling vesicular nano-carriers created from hydrating non-ionic surfactant, cholesterol, or amphiphilic compounds along comprehensive applications such as transdermal and brain-targeted delivery.

Antibiotic Release and Mechanical Performance of Polymethylmethacrylate (PMMA) Bone Cement: Findings from In-vitro Studies

Using Polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in-vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance. Using Polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in-vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance.

Computational Study on the Photo‐Induced Antibiotic Activity of an Azoquinolone with Promising Applications in Photopharmacology

Azocompounds are among the most important group of molecular photoswitches due to their multiple applications in various scientific areas. We studied the thermal and photochemical reactions of an azocompound with photo‐induced antibiotic properties using ab‐initio calculations based on Kohn‐Shan, Spin‐Flip and time‐dependent Density Functional Theory. Our primary goal is to understand the absorption spectra and isomerization pathways governing the molecule’s light‐controlled antibiotic activity. The nuclear ensemble approach was used for the most stable trans and cis isomers, and the absorption spectra were calculated and fitted to predict the cis/trans isomer ratios in the carboxylate form, using experimental measurements as a reference. We stablished that rotation is involved in the most favorable cis⇄cis and trans⇄trans thermal isomerization pathways, while the inversion mechanism is the most likely for cis⇄trans isomerizations. We found that the photochemical trans→cis isomerization follows a consistent mechanism across all trans isomers, involving excitation to S2(ππ*), an in‐plane ultrafast internal conversion to S1(nπ*), followed by rotation of the azo bond up to a twisted S1(nπ*)/S0 conical intersection. We used a custom approach to evaluate the most favorable decay pathway from the S1(nπ*)/S0 conical intersections to trans and cis photoproducts using static calculations.

Curcuma longa essential oil as an acaricidal agent for the control of cattle ectoparasitic tick - Rhipicephalus (Boophilus) annulatus

well known for its insecticidal, anti-inflammatory, antioxidant, anticancer, anti-rheumatic and antibiotic properties, Turmeric (Curcuma longa L.) Essential oil (EO), is effective in repelling and controlling many different pest species. The present study evaluates in vitro efficacy of turmeric EO against ectoparasitic tick, Rhipicephalus (Boophilus)annulatus collected from their natural host, domesticated cows. Repellency and toxicity of the EO on ectoparasitic ticks was analyzed with petri dish choice bioassay and AIT (Adult immersion test) against adult engorged females and nymphal stages of ticks. The Repellency Concentration (RC50) and Lethal Concentration (LC50) reproductive index, inhibition of oviposition and egg hatchability of treated ticks were estimated. GC-MS analysis identified Ar-turmerone as the major phytochemical, which induces adulticidal and repellant properties of EO. The nymphal stages of the ticks exhibited greater repellency on application of EO than the adult stage. Also, EO induced effective mortality in adult ticks. Further, this lethal concentration is capable of producing a decreased output in reproductive parameters namely, fecundity, % of oviposition and egg hatchability in surviving ticks thereby considerably reducing Rhipicephalus (Boophilus) R(B). annulatus population on its host. This study reveals the potency C. longa EO to be used as an effective pest control agent against R (B). annulatus infestation that can serve as an alternative to synthetic pesticides.

Antibiotic resistance genes, colistin-resistant Escherichia coli, and physicochemicals in health care wastewater in Vinh Long General Hospital, Vietnam.

This study collected ten treated wastewater samples from Vinh Long General Hospital to determine their physicochemical characteristics and antibiotic properties. All treated wastewater samples collected during the monitoring periods complied with national regulations. In addition, these samples did not contain bacteria such as Salmonella, Shigella, and Vibrio cholerae. The investigation yielded a total of 25 Escherichia coli isolates. The E. coli isolates exhibied highest antibiotic resistance rate to ampicillin (100%), followed by ciprofloxacin, amoxicillin/clavulanic acid, and cefazolin (96%, 92%, and 92%, respectively). The resistance rate to fosfomycin was 88%, whereas 80% of the isolates were resistant to sulfamethoxazole-trimethoprim. The resistance rate to gentamicin was 72%, whereas that to imipenem and tetracycline was 52%. In addition, 44% isolates were resistant to chloramphenicol, and 32% of isolates were colistin-resistant. Among analyzed isolates, three were resistant to 10 of 11 tested antibiotics but only displayed intermediate resistance to imipenems (carbapenems). Surprisingly, 23 out of 25 isolates showed a positive ESBL phenotype. Eleven of them had both the blaTEM and blaCTX-M-1 group structural genes, while twelve only had the blaCTX-M-1 group gene. Furthermore, none of the isolated E. coli isolates exhibited the blaSHV gene. The minimum inhibitory concentration (MIC) of colistin exceeded 4μg/mL in 8 out of 25 (32%) isolates. Seven of eight isolates (87.5%) carried the mcr-1 gene, while one (12.5%) carried the mcr-8 gene. None of the other mcr (mcr-2 to mcr-9) genes were found.

<i>Grewia asiatica</i>: An In-depth Analysis of its Phytochemical Composition, Antioxidant Potency, and Implications in Cancer Therapeutics

Background: Cancer is a global health issue, and natural medicinal plants like Grewia asiatica, also known as ‘Phalsa’, offer a promising alternative to synthetic medications due to their antipyretic, antidiabetic, analgesic, antibiotic, and antimicrobial properties. G. asiatica leaves possess a wide range of therapeutic actions like antipyretic, antidiabetic, antibiotic, and anticancer properties. Aim: This study aimed to explore the pharmacognostic characteristics, phytochemical composition, in vitro antioxidant activity, and anticancer potential of G. asiatica leaves. Methods: G. asiatica leaves, pharmacognostical, phytochemical and proximal analysis were carried out by standard qualitative and quantitative methods. The antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay and Ferric Reducing Antioxidant Power (FRAP) assay whereas anticancer activity was determined using five different human cancer cell line (DU-145, MDA-MB-231, HT-29, SK-OV-3, A-549) by SRB assay. Results: The micromorphological evaluation of G. asiatica leaves revealed unique characteristics, aiding in species identification. Physicochemical parameters, including total ash and extractive values, assessed quality control. Preliminary phytochemical screening identified alkaloids, flavonoids, and glycosides. Quantitative analysis demonstrated a total phenolic content of 20.19 ± 1.34 mg gallic acid equivalent/g in EEGA, emphasizing its potential antioxidant properties. The total flavonoid content was 7.59 ± 0.71 mg rutin equivalent/g, further supporting the antioxidant potential. In vitro antioxidant assays, including DPPH and FRAP, confirmed EEGA’s strong scavenging activity and reducing power. In vitro cytotoxicity studies using five human cancer cell lines revealed minimal cytotoxic effects, with GI50 values exceeding 80 μg/mL. Conclusion: The study provides comprehensive insights into the micromorphological, phytochemical profile and antioxidant properties of G. asiatica leaves. While exhibiting promising antioxidant activity, further research is warranted to explore its anticancer potential at higher concentrations. The findings underscore the importance of G. asiatica leaves as a potential source of natural antioxidants and warrant further investigation for its role in cancer prevention and treatment.