Potent Antibacterial Activity Research Articles

Pyridazinone-based derivatives as anticancer agents endowed with anti-microbial activity: molecular design, synthesis, and biological investigation.

Cancer patients undergoing chemotherapy are highly susceptible to infections owing to their compromised immune system, which also promotes cancer progression through inflammation. Thus, this study aimed to develop novel chemotherapeutic agents with both anticancer and antimicrobial properties. A series of diarylurea derivatives based on pyridazinone scaffolds were designed, synthesized, and characterized as surrogates for sorafenib. The synthesized compounds were tested for their antimicrobial activity and screened against 60 cancer cell lines at the National Cancer Institute (NCI). Compound 10h exhibited potent antibacterial activity against Staphylococcus aureus (MIC = 16 μg mL-1), whereas compound 8g showed significant antifungal activity against Candida albicans (MIC = 16 μg mL-1). Additionally, ten compounds were further evaluated for VEGFR-2 inhibition, with compound 17a showing the best inhibitory activity. Compounds 8f, 10l, and 17a demonstrated significant anticancer activity against melanoma, NSCLC, prostate cancer, and colon cancer, with growth inhibition percentages (GI%) ranging from 62.21% to 100.14%. Compounds 10l and 17a were selected for five-dose screening, displaying GI50 values of 1.66-100 μM. Compound 10l induced G0-G1 phase cell cycle arrest in the A549/ATCC cell line, increasing the cell population from 85.41% to 90.86%. Gene expression analysis showed that compound 10l upregulated pro-apoptotic genes p53 and Bax and downregulated the anti-apoptotic gene Bcl-2. Molecular docking studies provided insights into the binding modes of the compounds to the VEGFR-2 enzyme. In conclusion, the pyridazinone-based diarylurea derivatives developed in this study show promise as dual-function antimicrobial and anticancer agents, warranting further investigation.

Peptide PaDBS1R6 has potent antibacterial activity on clinical bacterial isolates and integrates an immunomodulatory peptide fragment within its sequence

BackgroundResistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges. Major conclusionsHere we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 μmol L−1. It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties. General significanceThis study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs.

Real-time monitoring of peptic and tryptic digestions of immunoglobulin G and the impact of dietary hydrocolloids on digestion

Immunoglobulin G (IgG) exhibits potent antiviral, antibacterial, and immunological activities. The digestion process and bioavailability of IgG are often a concern. Dietary hydrocolloids are crucial for regulating healthy digestion and the bioavailability of protein as functional components. Understanding the effects of dietary hydrocolloids on the digestive kinetics of IgG is requisite. Herein, the pepsin and trypsin digestion of IgG was investigated using ordered porous layer interferometry (OPLI). The real-time variation in the interference spectral shift reflected by OPLI can be converted into changes in the optical thickness (OT) to obtain a degradation kinetics curve. The impact of dietary hydrocolloids, including alginic acid sodium salt (ALG), polydextrose (PD), and konjac glucomannan (KG), on IgG degradation was evaluated using OPLI. The results demonstrated that ALG significantly inhibited the degradation of IgG by pepsin under acidic conditions, whereas the addition of PD increased the Michaelis–Menten constant for IgG degradation by trypsin. Notably, this dependence is not based on the hydrocolloid viscosity, but relies more on the electrical properties. The study enhances our understanding of how hydrocolloids affect IgG digestion and could provide valuable insights into preserving IgG activity and facilitating the development of oral drugs or health products related to IgG.

Nitrofuran Derivatives with Benzyl Groups are Promising Candidates as Antibacterial Agents Against Staphylococcus epidermidis

AbstractStaphylococcus epidermidis is a particular concern due to its high resistance to most antibiotics. We designed and synthesised a series of nitrofuran derivatives based on the chemical structure of nitrofurantoin. Among these derivatives, compared to nitrofurantoin, the nitrofuran derivatives with n‐alkyl groups did not effectively inhibit S. aureus with minimum inhibitory concentrations (MIC) values ranging from 16 to >128 μM, while these with benzyl groups displayed potent antibacterial activity against S. aureus with MIC values ranging from 4 to 16 μM. It suggests benzyl groups play an important role in the nitrofuran derivatives against S. aureus. The nitrofuran derivatives with benzyl groups also displayed potent antibacterial activity against S. epidermidis with MIC values ranging from 2 to 8 μM. Especially, compound 20 exhibited MIC 2 μM (0.814 μg/mL) against S. epidermidis. The CC50s of compound 20 in 293 T cells and LX‐2 cells were 3.131 μg/mL and 30.51 μg/mL, respectively. While at 128 μg/mL of compound 20, no obvious red blood cell rupture was observed. It showed minimal cytotoxicity and hemolytic activity. These findings suggest that compound 20 could function as a potential antibacterial agent for treating Urinary tract infections (UTIs) caused by S. epidermidis.

Photothermal Antibacterial and Osteoinductive Polypyrrole@Cu Implants for Biological Tissue Replacement.

The treatment of bone defects caused by disease or accidents through the use of implants presents significant clinical challenges. After clinical implantation, these materials attract and accumulate bacteria and hinder the integration of the implant with bone tissue due to the lack of osteoinductive properties, both of which can cause postoperative infection and even lead to the eventual failure of the operation. This work successfully prepared a novel biomaterial coating with multiple antibacterial mechanisms for potent and durable and osteoinductive biological tissue replacement by pulsed PED (electrochemical deposition). By effectively regulating PPy (polypyrrole), the uniform composite coating achieved sound physiological stability. Furthermore, the photothermal analysis showcased exceptional potent photothermal antibacterial activity. The antibacterial assessments revealed a bacterial eradication rate of 100% for the PPy@Cu/PD composite coating following a 24 h incubation. Upon the introduction of NIR (near-infrared) irradiation, the combined effects of multiple antibacterial mechanisms led to bacterial reduction rates of 99% for E. coli and 98% for S. aureus after a 6 h incubation. Additionally, the successful promotion of osteoblast proliferation was confirmed through the application of the osteoinductive drug PD (pamidronate disodium) on the composite coating's surface. Therefore, the antimicrobial Ti-based coatings with osteoinductive properties and potent and durable antibacterial properties could serve as ideal bone implants.

Green synthesis of zinc oxide nanoparticles from Wodyetia bifurcata fruit peel extract: multifaceted potential in wound healing, antimicrobial, antioxidant, and anticancer applications.

This study focuses on the synthesis, characterization, and use of zinc oxide nanoparticles (ZnONPs) derived from W. bifurcata fruit peel extract. ZnONPs are frequently synthesized utilizing a green technique that is both cost-effective and ecologically friendly. ZnONPs were characterized utilizing analytical techniques. Ultra Violet visible (UV-Vis) spectra showed peaks at 364nm, confirming the production of ZnONPs. Scanning Electron Microscope analysis indicated that the nanoparticles generated were spherical/agglomerated, with diameters ranging from 11 to 25nm. FTIR spectroscopy was used to identify the particular functional groups responsible for the nanoparticles' reduction, stabilization, and capping. Phytochemical analysis of the extract revealed that flavonoids, saponins, steroids, triterpenoids, and resins were present. The antibacterial activity of W. bifurcata synthesised nanoparticles was evaluated against pathogenic bacteria. The ZnONPs antioxidant activity was assessed using DPPH assay. The in vitro cytotoxicity was assessed against prostate cancer PC3 cells. The wound healing potential was assessed by employing in vitro scratch assay and in vivo excision model in Wistar rats. Because of its environmentally benign production, low toxicity, and biocompatibility, ZnONPs exhibited potential antibacterial, antioxidant, anticancer, and wound healing activities, indicating that they could be used in cancer treatment and wound management. Further study is required to examine the fundamental mechanisms and evaluate the safety and effectiveness of the test sample in clinical situations.

Identification, Characterization, and Antibacterial Evaluation of Five Endophytic Fungi from Psychotria poeppigiana Müll. Arg., an Amazon Plant.

Endophytic fungi, residing within plants without causing disease, are known for their ability to produce bioactive metabolites with diverse properties such as antibacterial, antioxidant, and antifungal activities, while also influencing plant defense mechanisms. In this study, five novel endophytic fungi species were isolated from the leaves of Psychotria poeppigiana Müll. Arg., a plant from the Rubiaceae family, collected in the tropical Amazon region of Bolivia. The endophytic fungi were identified as a Neopestalotiopsis sp., three Penicillium sp., and an Aspergillus sp. through 18S ribosomal RNA sequencing and NCBI-BLAST analysis. Chemical profiling revealed that their extracts obtained by ethyl acetate contained terpenes, flavonoids, and phenolic compounds. In a bioautography study, the terpenes showed high antimicrobial activity against Escherichia coli. Notably, extracts from the three Penicillium species exhibited potent antibacterial activity, with minimum inhibitory concentration (MIC) values ranging from 62.5 to 2000 µg/mL against all three pathogens: Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (both Gram-positive and Gram-negative bacteria). These findings highlight the potential of these endophytic fungi, especially Penicillium species as valuable sources of secondary metabolites with significant antibacterial activities, suggesting promising applications in medicine, pharmaceuticals, agriculture, and environmental technologies.

Elucidating study of “Eri” and Cannabis sativa: An antibacterial approach via B/nZVCu-M NPs fabrication

Nowadays, the search for futuristic textiles has been increasing rapidly to satisfy consumer notions. These textiles can retain moisture which may lead to harmful bacterial growth. To address this problem, nanoparticle coating plays a significant role exploring antibacterial efficacy. This study aims to address the antibacterial activity of specific strains by bentonite supported bimetallic nanoparticles. B/nZVCu-M NPs was synthesized using various parts of Cannabis sativa extract (stem, seeds and leaves) in aqueous media. A notable color change was observed within ±3 min confirming the formation of B/nZVCu-M NPs which was characterized using different techniques. The bioactive phytochemicals was successfully analyzed by GC–MS. The average size in relation to PXRD and SEM ranges from18–21 nm. XPS revealed the formation of M0 NPs. B/nZVCu-Zn NPs (Stem) has the highest surface area of 55.25m2/g which is the most thermally stable. “Eri” silk was transformed into nano-fabric by coating with B/nZVCu-M NPs which was later evaluated for antibacterial activity against Bacillus thuringiensis. The results revealed that exhibit potent antibacterial activity for B/nZVCu-Zn NPs (Stem) and B/nZVCu-Ag NPs (Leaves) with ZOI of 24.3 mm. A rapid decrease in optical density count and most number of cell colony count was seen in B/nZVCu-Zn NPs (Stem), proving to be best bacterial resistant material. The significant studies revealed B/nZVCu-Zn NPs (Stem) to be the most significant relating to all the antibacterial analyses.

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.

Bioengineered FeZn/GA@Cu nanocomposite utilizing spent coffee ground extract and gum arabic: Enhanced nitrate removal via (RSM) and machine learning optimization

This research focused on synthesizing an eco-friendly FeZn/GA@Cu nanocomposite using spent coffee grounds and Gum Arabic (GA). The study aimed to investigate its effectiveness as both a photocatalyst and an adsorbent, specifically for removing nitrates from aqueous solutions. The prepared nanocomposite was characterized using various analytical techniques, including XRD, TGA, FESEM with EDS, TEM, BET, FTIR, zeta potential, UV-DRS, and VSM. The RSM method, an impressive removal efficiency of 95.28 % for nitrate was projected under the specific conditions of an optimal dose of 1.82 g/L, an initial concentration of 60.00 mg/L, a pH level of 5.85, and a reaction duration of 48.90 min. It was ascertained that the peak efficiency of 98.25 % could be achieved with a carefully calibrated dose of 1.94 g/L, an initial concentration of 62.69 mg/L, a pH of 5.16, and a reaction time contained within 45.75 min. The synthesized nanocomposites have shown potential antibacterial activity against gram+ve (Staphylococcus aureus) and gram-ve (Escherichia coli) pathogens. This study suggests that the FeZn/GA@Cu nanocomposite synthesized using spent coffee grounds has potential as a photocatalyst for removing nitrate from aqueous solutions.

D@MSNs-P/PCL antibacterial nanofibers combined with DBD cold plasma for fresh pork preservation

Fresh pork is easily contaminated by microorganisms, leading to spoilage. Dielectric barrier discharge (DBD) cold plasma technology has shown significant advantages in the preservation of meat. However, severe lipid oxidation of pork resulting from DBD treatment greatly limits its development. Herein, the antibacterial D@MSNs-P/PCL nanofiber membranes were prepared by modification polycaprolactone (PCL) with pre-reported nanomaterials (D@MSNs-P) through electrostatic spinning. Compared with the PCL membranes, the D@MSNs-P/PCL membranes showed better water stability, lower water vapor transmission rate, stronger hydrophobicity, and potent antibacterial activity. The D@MSNs-P/PCL membranes can be used for wrapping fresh pork before treatment with DBD plasma, which can not only improve the antibacterial efficiency but effectively inhibit the lipid oxidation and color change of fresh pork, extending the shelf life for 2 days. The developed D@MSNs-P/PCL membranes can also be used alone to preserve other fresh meat or oily food, with a wide range of application prospects.

Phytochemical and Pharmacological Profile of Desmodium gangeticum (L.) DC.: A Comprehensive Review

Abstract: Desmodium gangeticum (L.) DC., commonly known as Shalparni in Ayurveda, has been used for treating various diseases. The plant is one among ten ingredients of classical Ayurvedic formulations Dasamula. Decoctions of root and leaf, root powder and leaf juice of D. gangeticum are used as tonics, febrifuge, digestive, antiemetic, astringent, anti-asthmatic, anti-diarrhoeal and anti-inflammatory agents in traditional medicinal practices of India and its neighbouring countries. Phytochemical investigations of this plant revealed the presence of many bioactive phytoconstituents. The present review was prepared with the objective of documenting the phytochemical and pharmacological profiles of D. gangeticum. The data presented here were collected from various sources like books, journals, various online databases, and monographs and internet search engines Google Scholar, PubMed, Science Direct, etc. Studies reported from phytochemical screening revealed that D. Gangeticum leaves and roots are rich in flavonoids, alkaloids, terpenoids, tannins, phenols, carbohydrates, steroids, phenylpropanoids, pterocarpans, coumarins, and volatile oil. Among the isolated compounds, major bio-active constituents are alkaloids, flavonoids and pterocarpans. All these phytochemicals are widely distributed in various parts of D. gangeticum. The other active constituents like desmodin, hordenine and gangetin are largely responsible for its broad spectrum of therapeutic potentiality. Desmodin belongs to the class of pterocarpans and is reported to have antifungal and antibacterial activities. Gangetin, which also belongs to the pterocarpans, is reported to have anti-inflammatory and analgesic effects. FTIR spectroscopy showed that D. gangeticum extracts are mainly rich in phenolic derivatives. Scientific experiments carried out in vitro as well as preclinical animal experimentations, showed that the plant and its bioactive chemicals exhibit various therapeutic activities. It is reported that D. gangeticum extracts showed potent antioxidant, antibacterial, hypoglycaemic, analgesic, hepatoprotective, anti-inflammatory and antiarthritic activities. Studies reported that D. gangeticum or its formulations are safe when used in appropriate therapeutic dosage.

Ozenoxacin suppresses sebum production by inhibiting mTORC1 activation in differentiated hamster sebocytes.

Acne vulgaris is a complex condition involving factors that affect the pilosebaceous unit. A primary manifestation of acne pathology is the development of comedones, often linked to the overproduction of sebum resulting from 5α-dihydrotestosterone (5α-DHT) and insulin activity. Ozenoxacin is a topical quinolone that exhibits potent antibacterial activity against Cutibacterium acnes (C. acnes). It is commonly used to treat acne associated with this bacterium; however, its effect on sebum production within the sebaceous glands remains unclear. In this study, the effects of ozenoxacin on sebum production were examined using insulin- and 5α-DHT-differentiated hamster sebocytes. Ozenoxacin showed a dose-dependent inhibition of lipid droplet formation and triacylglycerol (TG) production, which is a major component of sebum. In addition, it suppressed the expression of diacylglycerol acyltransferase 1, stearoyl-CoA desaturase-1, and perilipin-1 mRNA, all important factors involved in sebum synthesis, in a dose-dependent manner. Moreover, ozenoxacin decreased phosphorylated 40S ribosomal protein S6 levels downstream of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1), without altering the phosphorylation of Akt, an upstream regulator of mTORC1, in both insulin- and 5α-DHT-treated hamster sebocytes. Interestingly, nadifloxacin, but not clindamycin, exhibited a similar suppression of sebum production, albeit with lesser potency compared with ozenoxacin. Furthermore, a topical application of a 2% ozenoxacin-containing lotion to the auricle skin of hamsters did not affect the size of the sebaceous glands or epidermal thickness. Notably, it decreased the amount of TG on the skin surface. The results provide novel insights into the sebum-inhibitory properties of ozenoxacin, indicating its potential efficacy in controlling microbial growth and regulating sebum production for acne management.

An In Vitro and In Silico Study of Luteolin-Loaded Zinc Oxide Nanoparticles: Enhancing Bioactivity and Efficacy for Advanced Therapeutic Applications Against Cariogenic Microorganisms.

Introduction Recent studies have explored alternative methods to enhance caries prevention and treatment.Luteolin compound has been noted for its antimicrobial properties, while zinc nanoparticles (Zn NPs) are recognized for their potent antibacterial effects. This study investigates the synthesis, characterization, and antimicrobial efficacy of luteolin-loaded Zn oxide NPs (Luteo-ZnONPs) against cariogenic bacteria. By combining the biofilm-targeting capabilities of luteolin with the antimicrobial properties of Zn NPs, we aim to explore a novel approach for dental caries management. Methods Luteo-ZnONPswere synthesized and characterized using ultraviolet-visible (UV-vis) and Fourier transform infrared (FTIR) spectroscopy, confirming their successful formation and stability. Antimicrobial efficacy was assessed through minimum inhibitory concentration (MIC), demonstrating effectiveness against cariogenic bacteria such asEscherichia coli,Enterococcus faecalis, Pseudomonas aeruginosa, and Streptococcus mutans in different concentrations.The agar well plate method was employed to analyze the growth inhibitory effect of Luteo-ZnONPs (50 and 100µg/ml, respectively). Streptomycin (100µg/ml) was used as apositive control. The results (zone of inhibition (ZOI) in millimeter, mm) were represented as mean± standard deviation.One-way analysis of variance (ANOVA) was employed to detect the significance (p < 0.05) between the groups. Cytotoxicity was analyzed using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assayagainst MG63 cells, and doxorubicin was used as a positive control.Wilcoxon rank test was used for the statistical method. Gyrase Bwas downloaded from Protein Data Bank (PDB id: 6F86) and docked against luteolin using Autodock software (version 4.2).The binding score was presented as kcal/mol in table format. Results Characterization results showed that UV-vis spectroscopy revealed characteristic peaks, indicating the successful synthesis and stability of Luteo-ZnONPs. FTIRspectroscopy confirmed the presence of functional groups from luteolin compound interacting with the Zn NPs. It showed effective inhibition againstE. coli on 50µg/ml as 12.45 mm as ZOI and increased with concentration (100 µg/ml as 17.13 mm).It showed minimal ZOI onE. faecalis(8.12, 12.21 on 50 and 100µg/ml, respectively). The cytotoxicity of Luteo-ZnONPs was lesser than doxorubicin on MG63 cells with statistical high significance (p < 0.0014). These results showed thatLuteo-ZnONPs had effective antimicrobial nature againstEnterococcusfamily. Thus, gyrase BfromE. coliwas selected for the molecular docking analysis. The catalytic tunnel in gyrase B (E. coli, PDB: 6F86), influenced by Luteo-ZnONPs, indicated potential for novel, broad-spectrum antimicrobials via selective inhibition at conserved active sites. Conclusion The agar well plate and MIC confirmed that Luteo-ZnONPs exhibited potent antibacterial activity, especiallyat higher concentrations compared to streptomycin.One- way ANOVA demonstrated significant differences in antibacterial efficacy between treatments, validating its superior performance.Its strong interaction onin silicolevel showed the targeted mechanism of action. Luteo-ZnONPs showed lesser toxicity than doxorubicin on MG63 cells. These findings underscore the potential of its broad spectrum antimicrobial nature paving the way for its development into innovative, nontoxic therapeutic solutions.

Optimizing physicochemical properties, antioxidant potential, and antibacterial activity of dry ginger extract using sonication treatment

This research paper focused on enhancing the physico-chemical attributes, antioxidant capacity, and antibacterial effectiveness of dry ginger extract through sonication as an assistant extraction treatment. Ginger, resulting from the rhizome of Zingiber officinale Roscoe, is known for its culinary and medicinal uses outstanding to its antioxidant and antimicrobial possessions from phenolic acids and flavonoids. The study explored the use of sonication as an assistant extraction method and found that it significantly augmented the total phenolic content of the ginger extract by 28 % compared to traditional extraction methods, reaching 10.55 ± 1.50 mg GAE/g, DW. The research assessed the physicochemical belongings, antioxidant action, and antibacterial possibility of the sonicated ginger extract. The sonicated extract exhibited scavenging activity against the DPPH radical of 56.0 %. Pearson correlation investigation revealed a strong confident correlation between the phenolic content and antioxidant activity (r = 0.92, p < 0.01), as well as volatile compounds exhibited a moderate confident correlation with antibacterial action (r = 0.67, p < 0.05). The sonicated ginger extract also demonstrated potent antibacterial action, preventing the growth of both Gram-positive and Gram-negative bacteria. These findings contribute to the development of more efficient methods for extracting phenolic from ginger and provide insights into the relationships between phenolic and bioactive properties.

Evaluation of the antibacterial effect of (R)-(+)-Limonene against Enterococcus faecalis and Enterobacter cloacae strains isolated from food

The aim of this study was to evaluate the potential antibacterial and anti-adherent activities of the monoterpene (R)-(+)-limonene, as well as its synergistic potential with synthetic antimicrobials against strains of Enterococcus faecalis and Enterobacter cloacae. The antibacterial properties of (R)-(+)-limonene were assessed using the broth microdilution technique to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, the infusion disc method was employed to explore the association of the compound with antimicrobials, and the test tube method was used to determine the minimum inhibitory concentration of adherence (MICA). It was observed that the MIC for (R)-(+)-limonene was 1000 μg mL-1 for five of the six E. faecalis strains tested, while for E. cloacae, the MIC exceeded 1000 μg mL-1 for all strains tested. Identical values were recorded for the MBC in E. faecalis. In terms of its combination with synthetic antimicrobials, (R)-(+)-limonene demonstrated a synergistic effect with gentamicin and ciprofloxacin for most strains. Regarding the MICA, both (R)-(+)-limonene and 0.12% chlorhexidine digluconate failed to inhibit biofilm formation at the tested concentrations. Given the need for new therapeutic alternatives for treating bacterial infections, this study revealed that the tested monoterpene exhibited moderate bactericidal effects against E. faecalis strains and no antibacterial effect against E. cloacae strains. However, when combined with various classes of antimicrobials, (R)-(+)-limonene showed synergistic effects with gentamicin and ciprofloxacin for most strains. This suggests that (R)-(+)-limonene holds promise for enhancing the treatment of bacterial infections and could support conventional therapies. Nonetheless, further in vitro, ex vivo, and in vivo studies are necessary to confirm and elucidate its efficacy and mechanisms.

Synthesis and evaluation of di-heterocyclic benzazole compounds as potential antibacterial and anti-biofilm agents against Staphylococcus aureus.

Cumulative escalation in antibiotic-resistant pathogens necessitates the quest for novel antimicrobial agents, as current options continue to diminish bacterial resistance. Herein, we report the synthesis of di-heterocyclic benzazole structures (12-19) and their invitro evaluation for some biological activities. Compounds 16 and 17 demonstrated potent antibacterial activity (MIC = 7.81 μg/mL) against Staphylococcus aureus, along with significant anti-biofilm activity. Noteworthy is the capability of Compound 17 to inhibit biofilm formation by at least 50% at sub-MIC (3.90 μg/mL) concentration. Furthermore, both compounds exhibited the potential to inhibit preformed biofilm by at least 50% at the MIC concentration (7.81 μg/mL). Additionally, Compounds 16 and 17 were examined for cytotoxic effects in HFF-1 cells, using the MTT method, and screened for binding interactions within the active site of S. aureus DNA gyrase using in silico molecular docking technique, employing AutoDock 4.2.6 and Schrödinger Glidse programs. Overall, our findings highlight Compounds 16 and 17 as promising scaffolds warranting further optimization for the development of effective antibacterial and anti-biofilm agents.

Computational study of phytochemical derived bioactive compounds of Vernonia amygdalina as a potential inhibitor of Topoisomerase IV in pneumonia

Several of the bacteria responsible for pneumonia had become resistant to available antibiotics. According to the WHO, the resistance of Klebsiella pneumonia to Ciprofloxacin is 79.4%, making infections such as pneumonia and several diseases more difficult, if not impossible to treat. The prevalence of antimicrobial resistance is a global problem and among the 10 top global health threats facing humanity. With the projection of 10 million deaths per year by 2050 due to bacterial infections associated with antibiotic resistance according to WHO, there is an urgent need to identify an alternative approach to curb the incessant antimicrobial resistance and a complementary approach is to employ the use of naturally occurring compounds with potent antibacterial activities. We employed structural bioinformatics and theoretical chemistry techniques via molecular docking, and pharmacokinetic study, to identify novel S. pneumoniae topoisomerase IV inhibitors. The stringent molecular docking identified Arg140, Arg81, Glu55, Pro84, Met83, and Asn51, as principal amino acid residues for topoisomerase IV ligand interactions. Ten of the bioactive compounds found in Vernonia amygdalina showed a higher binding energy when compared to the reference compound (Ciprofloxacin). The overall analysis of MD results and binding free energy calculations reveal that Luteolin and 7-O-methylwogonin displayed stable trajectories with acceptable RMSD values and sufficient high negative energies throughout the MD simulation run of 100ns. These identified bioactive compounds in this study can be taken further for in vitro and In vivo studies to examine their efficacy against Pneumonia.

Chemical Composition and Antibacterial, Antioxidant, and Cytotoxic Activities of Essential Oils from Leaves and Stems of Aeschynomene indica L.

The objective of this study was to analyze the chemical composition and evaluate the biological capabilities of the essential oils (EOs) extracted from leaves and stems of wild Aeschynomene indica L. plants by the hydrodistillation method. By using GC-FID/MS, fifty-six and fifty-five compounds, representing 95.1 and 97.6% of the essential oils in the leaves and stems, respectively, were characterized. The predominant constituents of A. indica EOs were (E)-caryophyllene, linalool, viridiflorol, phytol, hexadecanoic acid, trans-verbenol, and α-guaiene. The antibacterial and synergistic activities of the EOs were assessed by microdilution and checkerboard assays. The results revealed a potent inhibition and bactericidal activity against Staphylococcus aureus and Bacillus subtilis with MICs of 0.312-0.625 mg/mL. When combined with traditional antibiotics, the essential oils of A. indica possessed excellent synergistic effects against all tested bacteria. Additionally, the EOs of A. indica leaves showed higher antioxidant activity (IC50 = 0.11 ± 0.01 µg/mL) compared to the stem oil (IC50 = 0.19 ± 0.01 µg/mL) using the ABTS radical scavenging assay. The in vitro cytotoxicity of EOs against human cancer cell lines HepG2, MCF-7, A-549, and HCT-116 was examined, and MTT assays showed that the EOs possessed a significant cytotoxic potential against MCF-7 breast cancer cells, with IC50 values of 10.04 ± 1.82 and 15.89 ± 1.66 μg/mL, and a moderate cytotoxic activity against other tested cells. In conclusion, the A. indica EOs could be considered a potential source of pharmacologically active compounds.

AI-guided few-shot inverse design of HDP-mimicking polymers against drug-resistant bacteria

Host defense peptide (HDP)-mimicking polymers are promising therapeutic alternatives to antibiotics and have large-scale untapped potential. Artificial intelligence (AI) exhibits promising performance on large-scale chemical-content design, however, existing AI methods face difficulties on scarcity data in each family of HDP-mimicking polymers (<102), much smaller than public polymer datasets (>105), and multi-constraints on properties and structures when exploring high-dimensional polymer space. Herein, we develop a universal AI-guided few-shot inverse design framework by designing multi-modal representations to enrich polymer information for predictions and creating a graph grammar distillation for chemical space restriction to improve the efficiency of multi-constrained polymer generation with reinforcement learning. Exampled with HDP-mimicking β-amino acid polymers, we successfully simulate predictions of over 105 polymers and identify 83 optimal polymers. Furthermore, we synthesize an optimal polymer DM0.8iPen0.2 and find that this polymer exhibits broad-spectrum and potent antibacterial activity against multiple clinically isolated antibiotic-resistant pathogens, validating the effectiveness of AI-guided design strategy.