Highest Inhibitory Activity Research Articles

Selective Covalent Inhibiting JNK3 by Small Molecules for Parkinson's Diseases.

c-Jun N-terminal kinases (JNKs) including JNK1/2/3 are key members of mitogen-activated protein kinase family. Wherein JNK3 is specifically expressed in brain and emerges as therapeutic target, especially for neurodegenerative diseases. However, developing JNK3 selective inhibitors as chemical probes to investigate its therapeutic potential in diseases remains challenging. Here, we adopted the covalent strategy for identifying JNK3-selective covalent inhibitorJC16I, with high inhibitory activity against JNK3. Despite targeting a conserved cysteine the vicinity of ATP pocket in JNK family, JC16I exerted a greater than 160-fold selectivity for JNK3 over JNK1/2. Importantly, even at low concentration, JC16I showed enhanced and long-lasting inhibition against cellular JNK3. In addition, its alkyne-containing probe JC-P1 could label JNK3 in SH-SY5Y cell lysate and living cells, with goodproteome-wide selectivity. Furthermore, JC16I selectively suppressed the abnormal activation of JNK3 signaling and sufficiently exhibited neuroprotective effect in Parkinson's diseases (PD) models. Overall, our findings highlight the potential of developing isoform-selective and cell-active JNK3 inhibitors by covalent drug design strategy targeting a conserved cysteine. This work not only provides a valuable chemical probe for JNK3-targeted investigations in vitro and in vivo but also opens new avenues for the treatment of PD.

Synthesis and immunotherapy efficacy of a PD-L1 small-molecule inhibitor combined with its 131I-iodide labelled isostructural compound

Although antibody-based immune checkpoint blockades have been successfully used in antitumor immunotherapy, the low response rate is currently the main problem. In this work, a small-molecule programmed cell death-ligand (PD-L1) inhibitor, LG-12, was developed and radiolabeled with 131I to obtain the chemically and biologically identical radiopharmaceutical [131I]LG-12, which aimed to improve the antitumor effect by combination of LG-12 and [131I]LG-12. LG-12 showed high inhibitory activity to PD-1/PD-L1 interaction. The results of cell uptake and biodistribution studies indicated that [131I]LG-12 could specifically bind to PD-L1 in B16-F10 tumors. It could induce immunogenic cell death and the release of high mobility group box 1 and calreticulin. The combination of [131I]LG-12 and LG-12 could significantly inhibit tumor growth and resulted in enhanced antitumor immune response. This PD-L1 small-molecule inhibitor based combination strategy has great potential for tumor treatment.

Experimental, Density Functional Theory, Molecular Docking and ADMET Analyses on the Role of Different Plant Extracts of Aronia melanocarpa (Michx) Elliot Species on Acetylcholinesterase Enzyme Activity

In the present study, different extracts obtained in different solvents from the fruits collected from the Aronia melanocarpa (Michx.) were prepared. The inhibition performances of these extracts on the inhibition of the acetylcholinesterase enzyme were checked via both theoretical and experimental analyses. Although all extracts used in experimental studies showed high inhibitory activity, it was observed that the extract obtained in methanol had higher inhibitory activity than the others. According to the enzyme activity results presented in the light of Ellman method, IC50 values were found between 0.0311-0.0857 mg/mL. Conceptual Density Functional Theory (CDFT) and Molecular Docking calculations were performed to identify the component or components of the extract with high inhibitory activity. Conceptual Density Functional Theoretical based data commented through popular electronic structure principles such as Maximum Hardness and Minimum Electrophilicity Principles showed that the most reactive one among studied dominant components of the extract is Malvin molecule. The interactions between studied molecules and AChE and mechanisms of these interactions were illuminated via Molecular Docking analyses and ADMET studies. As a result, it was shown that the most reactive molecule Malvin (with lowest hardness and the highest electrophilicity) interacts more powerful with AChE compared to other molecules. Within the framework of the theoretical analyses made, it was proposed that in the design and introduction of new AChE inhibitors, structures with low hardness and high electrophilicity values ​​should be preferred.

Chemical Analysis and Biological Activities of Various Parts of Securidaca longipedunculata From South Africa

Objective The objective of our study was to investigate the chemical composition and the biological activities of different parts of Securidaca longipedunculata from South Africa. Methodologies The chemical analysis methods, including chromatography and spectroscopy, were employed to identify the diverse array of compounds present in the roots, leaves, and stems of S longipedunculata. Results The proximate analysis revealed that the leaf extracts had higher ( P < .05) crude protein, gross energy, and ether extract contents when compared to the stem bark and the root bark. A similar trend was observed with the mineral analysis where copper, iron, magnesium, and zinc were in abundance in the leaves. Concurrently, bioassays reveal significant biological activities, such as antioxidant, antimicrobial, and anti-inflammatory properties, associated with these plant parts. The extracts demonstrated high lipid peroxidation inhibitory activity at the concentration of 250 μg/mL, with the highest percentage inhibition of 94% recorded in the dark leaf extract, followed by 92% and 73% at the concentrations of 125 and 62.5 μg/mL, respectively. The antimicrobial analysis revealed that the root bark extract was active against Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis with the average minimum inhibitory concentration of 1.67 mg/mL (dark type) and 0.63 mg/mL (light type). Conclusion Our findings emphasize the medicinal potential of S longipedunculata and underscore the importance of understanding its chemical makeup in explaining its therapeutic effects. This research provides valuable insights into the pharmacological properties of S longipedunculata, offering a foundation for further exploration in drug development and natural product discovery.

Interventions based on alternative and sustainable strategies for postharvest control of anthracnose and maintain quality in tropical fruits.

Colletotrichum spp. is a phytopathogen causing anthracnose in a variety of tropical fruits. Strategies used to control postharvest diseases in tropical fruits typically rely on the use of synthetic fungicides, which have stimulated the emergence of resistant pathogens. Safer alternative strategies to control anthracnose in tropical fruits have been described in the literature. This review presents and discusses the main innovative interventions concerning the application of sustainable alternative strategies in the postharvest control of pathogenic Colletotrichum species in tropical fruits, with a particular emphasis on the studies published in the last 5 years. The available studies have shown the use of various methods, including physical barriers, natural antimicrobials, and biological control with antagonistic microorganisms, to reduce anthracnose lesion severity and incidence in tropical fruits. The available literature showed high inhibitory activity in vitro, reduced anthracnose incidence and lesion diameter, and total disease inhibition in tropical fruits. Most studies focused on the inhibition of Colletotrichum gloeosporioides on avocado, papaya, and mango, as well as of Colletotrichum musae on banana; however, the inhibition of other Colletotrichum species was also demonstrated. The application of emerging sustainable alternative methods, including natural antimicrobial substances, also stimulated the induction of defense systems in tropical fruits, including enzymatic activity, such as polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase. The retrieved data helped to understand the current state of the research field and reveal new perspectives on developing efficient and sustainable intervention strategies to control pathogenic Colletotrichum species and anthracnose development in tropical fruits.

The Use of Lemongrass/Lemon Blend Essential Oil Nanoemulsions in Chewy Candy Formulations and Its Evaluation Against Streptococcus mutans and Porphyromonas gingivalis

Lemongrass (Lg) and lemon (Lm) essential oils (EOs) mainly contain citral and limonene, respectively, which are not limited to flavor for food but can also provide antibacterial activity. The information on the enrichment of these combined EOs in chewy candy products has never been documented yet. This study aimed to evaluate the physical-chemical properties and volatile compound of nanoemulsion formulations of Lg/Lm blend EOs as well as the physical-chemical properties, total plate count (TPC), and sensory acceptability of chewy candy formulated with nanoemulsions. Antibacterial evaluations against Streptococcus mutans and Porphyromonas gingivalis were performed for both nanoemulsion and chewy candy. Blending Lg and Lm EOs at ratios of Lg1.85 : Lm2.25 and Lg3.65 : Lm0.45 showed a broadly different constituent of the volatile compound than the ratio with the least amount of Lg (Lg0.05 : Lm4.05) but all the formulations possessed eugenol, β-Bisabolene, and caryophyllene oxide. The combination of Lg1.85 : Lm2.25 produced the nanoemulsion with the lowest particle size but lower zeta potential and emulsion stability. At this ratio, the significant inhibitory activity of the nanoemulsion was found to be 92.40% and 84.14% for S. mutans and P. gingivalis, respectively (p < 0.05). Its application in chewy candy formulation also resulted in the highest inhibitory activity against S. mutans (85%) and P. gingivalis (77.20%). Chewy candy formulated with Lg1.85 : Lm2.25 nanoemulsion was also found to have the lowest TPC of 3.72 log CFU/g. The overall acceptability of the chewy candy was around neutral (3.77) by panelists for its higher color score (4.73) and aroma (4.37) in average to the other samples. This study discovered the potential of Lg/Lm blend EOs nanoemulsion for enhancing the antibacterial effect and improving the texture and color of chewy candy.

Discovery of the potent covalent inhibitor with an acrylate warhead for SARS-CoV-2 3CL protease

COVID-19 has caused severe consequences in terms of public health and economy worldwide since its outbreak in December 2019. SARS-CoV-2 3C-like protease (3CLpro), crucial for the viral replications, is an attractive target for the development of antiviral drugs. In this study, several kinds of Michael acceptor warheads were utilized to hunt for potent covalent inhibitors against 3CLpro. Meanwhile, novel 3CLpro inhibitors with the P3-3,5-dichloro-4-(2-(dimethylamino)ethoxy)phenyl moiety were designed and synthesized which may form salt bridge with residue Glu166. Among them, two compounds 12b and 12c exhibited high inhibitory activities against SARS-CoV-2 3CLpro. Further investigations suggested that 12b with an acrylate warhead displayed potent activity against HCoV-OC43 (EC50 = 97 nM) and SARS-CoV-2 replicon (EC50 = 45 nM) and low cytotoxicity (CC50 > 10 μM) in Huh7 cells. Taken together, this study devised two series of 3CLpro inhibitors and provided the potent SARS-CoV-2 3CLpro inhibitor (12b) which may be used for treating coronavirus infections.

Design, molecular docking, synthesis and in vitro evaluation of anti-influenza activity of oseltamivir carboxamides and their hybrid molecules with hydroxamic acid

Background The influenza virus is a highly contagious respiratory disease that causes seasonal outbreaks and occasionally, unpredictable pandemics with high morbidity and mortality rates. This problem is exacerbated by the lack of drugs with potential antiviral activity against all types of influenza strains, including resistant strains. Therefore, there is an urgent need to develop novel antiviral agents. Methods The synthesis of new oseltamivir carboxamides with amino acids and the subsequent synthesis of hybrid molecules with hydroxamic acid were considered. Two series are presented as series one; oseltamivir carboxamides with L-serine, L-isoleucine, L-phenylalanine, L-tyrosine and series two included hydroxamates of series one. This approach may provide promising candidates with potential anti-influenza activity. The in vitro cytotoxic activity against Madin-Darby Canine Kidney (MDCK), type (NBL-2) - CCL-34 cells using the MTT ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to determine the half maximal inhibitory concentrations (IC50) of the investigated compounds. The percent inhibition of neuraminidase was plotted against concentrations and the IC50 values were calculated by non-linear logistic curve fitting. Results The compounds were subjected to molecular docking using the GOLD suite (version 5.7.1) to predict the binding affinities for neuraminidase (3CL0). The docking scores are presented as PLP fitness and are comparable to those of oseltamivir. Oseltamivir-Phenylalanine recorded the highest docking score (72.23 kcal/mol), while, oseltamivir acid was recorded (56.24 kcal/mol). The ADMET parameters were generated using the Swiss ADME server to predict successful candidates with reasonable oral absorption and safety margins. All compounds are safer than oseltamivir and their IC50 values for neuraminidase inhibition were variable. The hybrids showed a lower percentage of viable cells. Oseltamivir-phenylalanine had the highest inhibitory activity against neuraminidase (3.03 μM), when compared with oseltamivir (67.22 μM). Conclusion Oseltamivir-phenylalanine showed remarkable and very significant activity, and the hybrid molecules were surprisingly less effective on neuraminidase than oseltamivir carboxamides.

WQ-3810, a fluoroquinolone with difluoropyridine derivative as the R1 group exerts high potency against quinolone-resistant Campylobacter jejuni.

WQ-3810, a relatively new quinolone antibiotic, demonstrates exceptional antibacterial properties against certain pathogens in previous studies. However, its efficacy against quinolone-resistant Campylobacter jejuni was not previously reported. The prevalence of quinolone-resistant C. jejuni as a cause of foodborne illnesses is increasing, prompting this investigation into the effectiveness of WQ-3810 as a countermeasure. This study revealed high inhibitory activity of WQ-3810 against both wild-type and mutant DNA gyrases of C. jejuni. WQ-3810 was equally efficacious as ciprofloxacin against wild-type DNA gyrases but showed superior effectiveness against mutant DNA gyrases. WQ-3810 also demonstrated the lowest minimum inhibitory concentrations, highlighting its enhanced potency against both susceptible and resistant strains of C. jejuni. This observation was well supported by the results of the in silico analysis. Consequently, WQ-3810 exhibits a higher level of bactericidal activity compared to existing quinolones in combating both susceptible and resistant C. jejuni isolates.

Anti-biofilm and anti-quorum sensing activities of extract, fractions and compounds from the leaves of Cassia alata L. against yeast pathogens

BackgroundCassia alata or Senna alata, also known as “ringworm bush” because of its very effective fungicidal properties, is commonly used in African traditional medicine to treat fungal infections. Despite extensive phytochemical and pharmacological studies previously reported on C. alata, the antibiofilm activity against pathogenic yeast as well as the related anti-quorum sensing mechanism of some active constituents has not yet been elucidated. The aim of the study was to isolate the bioactive constituents from the methanol extract of the leaves of C. alata (CAExt) using antibiofilm-guided fractionation against yeast fungal pathogens and then to investigate the anti-quorum sensing activity of the active constituents by assessing their ability to inhibit violacein production in Chromobacterium violaceum. MethodsChromatographic methods were used to isolate the constituents of CAExt, and spectroscopic methods were used to elucidate the chemical structures of the isolated compounds. The broth microdilution assay was used to evaluate the antifungal activity against Candida albicans and C. parapsilosis, while crystal violet staining was used for the inhibition of biofilm formation and the disruption of preformed biofilm. The biosensor strain C. violaceum ATCC 12472 was used to investigate the anti-quorum sensing activity of the most active constituents. ResultsThe crude extract exhibited biofilm inhibition and eradication activities against the tested pathogenic yeast. The biofilm inhibition percentages ranged from 53.22 % to 75.38 %, while the biofilm eradication percentages ranged from 23.21 % to 64.25 %. The ethyl acetate fraction demonstrated high biofilm inhibition and eradication activities against the tested microorganisms. The biofilm inhibition percentages ranged from 58.19 % to 79.30 %, while the biofilm eradication percentages ranged from 34.105 % to 69.54 %. The purification of subfractions led to the identification of six compounds: stigmasterol (1), sitosterol (2), lupeol (3), emodin (4), kaempferol (5) and stigmasterol glycoside (6), two of which (4 and 5) showed potent biofilm inhibition and eradication activities. Both compounds demonstrated significantly lower MBIC50 values of 70.81 µg/mL and 65.65 µg/mL against Candida albicans and MBEC50 values of 63.65 µg/mL and 82.66, respectively, against C. albicans and C. parapsilosis. The crude extract and compounds (4) and (5) also demonstrated quorum sensing inhibitory activity, as indicated by the MQSIC value of 1024 µg/mL for the crude extract and 128 µg/mL for the two compounds. Moreover, compounds (4) and (5) displayed significant inhibitory effects on violacein production, as indicated by their low IC50 values of 28.08 µg/mL and 26.44 µg/mL, respectively. ConclusionsData obtained in this study not only support the traditional use of C. alata in the treatment of fungal infections but also reveal C. alata extract, as well as the two isolated bioactive compounds emodin (4) and kaempferol (5), as a potential source for developing antibiofilm alternative agents against biofilm-associated yeast infections. List of compounds studiedstigmasterol (1), sitosterol (2), lupeol (3), emodin (4), kaempferol (5), stigmasterol glycoside (6)

Identification and molecular mechanism of novel hypoglycemic peptide in ripened pu-erh tea: Molecular docking, dynamic simulation, and cell experiments

Ripened pu-erh tea is known to have beneficial hypoglycemic properties. However, it remains unclear whether the bioactive peptides produced during fermentation are also related to hypoglycemic potential. This study aimed to identify hypoglycemic peptides in ripened pu-erh tea and to elucidate their bioactive mechanisms using physicochemical property prediction, molecular docking, molecular dynamics simulations, and cell experiments. Thirteen peptides were identified by liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS). Among them, AADTDYRFS (AS-9) and AGDGTPYVR (AR-9) exhibited high α-glucosidase inhibitory activity, with half-maximal inhibitory concentration (IC50) values of 0.820 and 3.942 mg/mL, respectively. Molecular docking and dynamics simulations revealed that hydrogen bonding, hydrophobic interactions, and van der Waals forces assist peptides AS-9 and AR-9 in forming stable and tight complexes with α-glucosidase. An insulin-resistance (IR)-HepG2 cell model was established. AS-9 was non-toxic to IR-HepG2 cells and significantly increased the glucose consumption capacity, hexokinase, and pyruvate kinase activities of IR-HepG2 cells (p < 0.05). AS-9 alleviated glucose metabolism disorders and ameliorated IR by activating the IRS-1/PI3K/Akt signaling pathway and increasing the expression levels of MDM2, IRS-1, Akt, PI3K, GLUT4, and GSK3β genes. In addition, no hemolysis of mice red blood cells red blood cells occurred at concentrations below 1 mg/mL. This work first explored hypoglycemic peptides in ripened pu-erh tea, providing novel insights for enhancing its functional value.

Design, synthesis and antimicrobial activity of novel berberine derivatives.

The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria. Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC50 value against Botrytis cinerea was 1.34 μg mL-1. Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC90 values of 3.12 μg mL-1 and 1.56 μg mL-1. A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight. This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry.

Isolation of the Endophytic Fungus Aspergillus terreus from a Halophyte (Tetraena qatarensis) and Assessment of Its Potential in Tomato Seedling Protection.

Living in diverse environmentally harsh conditions, the plant exhibits a unique survival mechanism. As a result, the endophytes residing within the plant produce specific compounds that promote the plant's growth and defend it against pathogens. Plants and algae symbiotically harbor endophytes, i.e., microbes and microorganisms living within them. The objective of this study is to isolate endophytic fungi, specifically strains of Aspergillus terreus, from the leaves of the salt-tolerant plant Tetraena qatarensis and to explore the salt tolerance, antagonistic activity, and growth promotion properties. Strain C A. terreus (ON117337.1) was screened for salt tolerance and antagonistic effects. Regarding salt tolerance, the isolate demonstrated the ability to thrive in a concentration of up to 10% NaCl. A. terreus showed inhibitory activity against four fungal phytopathogens, namely Fusarium oxysporum, Alternaria alternata, Colletotrichum gloeosporioides, and Botrytis cinerea. The GC-MS investigation of the fungal (strain C Aspergillus terreus) extract showed the presence of about 66 compounds (secondary metabolites). Secondary metabolites (SMs) are produced, like Hexadecanoic acid, which aids in controlling phytopathogens. Also produced is lovastatin, which is used to treat hypercholesterolemia. Strain C, which showed salinity tolerance and the highest inhibitory activity, was further analyzed for its effect on tomato seed germination under pathogen stress from Fusarium oxysporum. The greenhouse experiment indicated that the fungi increased the length of tomato seedlings and the plant biomass. Therefore, the selected endophytes derived from Tetraena qatarensis were scrutinized for their potential as biocontrol agents, aiming to thwart fungal pathogens and stimulate plant growth. The in vitro and in vivo assessments of strain C (Aspergillus terreus) against Fusarium oxysporum in this investigation indicate the promising role of endophytes as effective biological control agents. Investigating novel bio-products offers a sustainable approach to agriculture, gradually reducing dependence on chemical fungicides.

The inhibition of DPP-4 by Plantago asiatica L. and the discovery of active compounds

The objective of this study was to investigate the inhibitory effects of Plantago asiatica L. on DPP-4 and to determine the active compounds responsible for this inhibition. Extracts were prepared from the root and aerial portions of the plant using various polar solvents. The DPP-4 inhibition of these extracts was analyzed in an extracellular assay and then assigned to either the high or low inhibition group. The chemical profiles of these extracts were analyzed using an LC-MS method. The ion fragments that were potent in the high inhibition extracts were selected through OPLS-DA and correlation analysis, and then identified and obtained for verification of DPP-4 inhibition in both the extracellular assay and the Caco-2 cell line. The extracts showed various inhibitory activities with an average inhibition of 28.4 %. A total of 20 compounds were selected from the extracts with higher inhibitory activity and identified. Six of them, baicalein, scutellarein, calceolarioside B, isoacteoside, verbascoside, and plantamajoside, exhibited DPP-4 inhibition with IC50 values of 44.32, 59.90, 112.71, 157.02, 154.58, and 195.07 μg/mL, respectively, in extracellular assays. They also showed inhibition of DPP-4 on the Caco-2 cell line, with IC50 values of 31.56, 34.71, 20.29, 33.29, 24.52, and 87.88 μg/mL, respectively. The extracts from PAL showed inhibitory activity towards DPP-4, and the related compounds were identified and verified.

Antimicrobial activity of eight plant essential oils having antioxidant property against spoilage microbes.

To identify efficient, broad-spectrum, and non-toxic preservatives for natural agricultural products, eight essential oils were screened for high inhibitory and antioxidant activities against spoilage microbes. The zone of inhibition test and minimum inhibitory concentration (MIC) assay were performed to assess the antimicrobial activity of eight essential oils against Bacillus subtilis, Staphylococcus aureus, Penicillium, Saccharomyces, and Escherichia coli. Among the eight essential oils, garlic and rose essential oils exhibited the best inhibitory effects, their MICs against the spoilage microbes were 40-640 μl/l and 10-320 μl/l, respectively. In addition, the antioxidant activities of eight essential oils were compared using the DPPH and ABTS radical-scavenging assays and the reducing power assay. Eight essential oils had antioxidant capacity, among which rosemary, thyme, rose, and tea tree essential oils performed the best. Moreover, the combination of thyme and rose exerted stronger antioxidant activity. Therefore, the concentrations of rose and garlic, and thyme essential oils were optimized using response surface methodology to obtain the optimal composite ratios, which were 1254 μl/l, 640 μl/l, and 1228 μl/l for rose, garlic, and thyme, respectively. The DPPH free radical-scavenging rate detected using this formulation was 50.2%, basically consistent with the prediction. Zone of inhibition diameters with the compound essential oil, against five spoilage microbes, were all greater than 45mm. The essential oil combination had high antimicrobial, against agricultural product spoilage microbes, and antioxidant activities.

Bactofencin YH, a novel bacteriocin with high inhibitory activity against clinical Streptococcus species.

Strain Lactiplantibacillus plantarum D1 with bacteriocin producing ability was found in the intestine of Gambusia affinis. The bacteriocin was found to have high inhibitory activity against multiple Streptococcus species and several other Gram-positive and Gram-negative bacteria. Bacteriocin was purified from culture supernatant by ion-exchange chromatography, Sep-Pak C18 cartridge, and reverse-phase high-performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectral analysis determined that purified bacteriocin has a molecular mass of 2,731 Da. A partial N-terminal sequence KRKKHKXQIYNNGM was obtained from the Edman analysis. The N-terminal sequence was employed to search against a translation of the draft genome of strain D1. The translated full amino acid sequence of the mature peptide is as follows: NH2- KRKKHKCQIYNNGMPTGQYRWC, which has a molecular weight of 2738 Da. A BLAST search revealed that this bacteriocin was most similar to bactofencin A but differed from it with three amino acid residues. No identical peptide or protein has been previously reported, and this peptide, termed bactofencin YH, was therefore considered to be a new bacteriocin produced by Lactiplantibacillus plantarum D1.

Secondary metabolites in Cordyceps javanica with insecticidal potential

Cordyceps javanica has been registered as a fungal insecticide in several countries. However, little is known about whether metabolic toxins are involved in the insecticidal process. In this research, we assessed the insecticidal activity of the fermentation broth of C. javanica. Myzus persicae mortality differed when exposed to the metabolized C. javanica broths at 3 days post fermentation (DPF) and 5 DPF. Comparison of the metabolic fluid at 3 DPF and 5 DPF revealed a key alkaloid, heteratisine, which was found to have insecticidal activity and acetylcholinesterase (AChE) inhibitory activity. Heteratisine has high insecticidal activity against adult M. persicae, the absolute 50% lethal concentration (LC50) was only 0.2272 mg/L. Heteratisine showed high inhibitory activity on AChE with the 50% maximal inhibitory concentration (IC50) of 76.69 μM. Molecular docking and dynamic simulations showed that heteratisine conjugation occurs at the peripheral anionic site (PAS) of the AChE of M. persicae, leading to suppression of enzyme activity. Heteratisine was rarely found in fungal metabolites, which helps us to understand the complex and elaborate insecticidal mechanism of C. javanica.

Ecofriendly biosynthesis of copper nanoparticles from novel marine S. rhizophila species for enhanced antibiofilm, antimicrobial and antioxidant potential

Marine microorganisms offer a promising avenue for the eco-friendly synthesis of nanoparticles due to their unique biochemical capabilities and adaptability to various environments. This study focuses on exploring the potential of a marine bacterial species, Stenotrophomonas rhizophila BGNAK1, for the synthesis of biocompatible copper nanoparticles and their application for hindering biofilms formed by monomicrobial species. The study begins with the isolation of the novel marine S. rhizophila species from marine soil samples collected from the West coast region of Kerala, India. The isolated strain is identified through 16S rRNA gene sequencing and confirmed to be S. rhizophila species. Biosynthesis of copper nanoparticles using S. rhizophila results in the formation of nanoparticles with size of range 10–50 nm. The nanoparticles exhibit a face-centered cubic crystal structure of copper, as confirmed by X-Ray Diffraction analysis. Furthermore, the synthesized nanoparticles display significant antimicrobial activity against various pathogenic bacteria and yeast. The highest inhibitory activity was against Staphylococcus aureus with a zone of 27 ± 1.00 mm and the least activity was against Pseudomonas aeruginosa with a zone of 22 ± 0.50 mm. The zone of inhibition against Candida albicans was 16 ± 0.60 mm. The antibiofilm activity against biofilm-forming clinical pathogens was evidenced by the antibiofilm assay and SEM images. Additionally, the copper nanoparticles exhibit antioxidant activity, as evidenced by their scavenging ability against DPPH, hydroxyl, nitric oxide, and superoxide radicals, as well as their reducing power in the FRAP assay. The study highlights the potential of the marine bacterium S. rhizophila BGNAK1 for the eco-friendly biosynthesis of copper nanoparticles with diverse applications. Synthesized nanoparticles exhibit promising antibiofilm, antimicrobial, and antioxidant properties, suggesting their potential utility in various fields such as medicine, wastewater treatment, and environmental remediation.

An Integrated Metabolomics Study on Antidiabetic Activity of Christia vespertilionis Leaves Extract Using Chemometric and Molecular Docking Analysis.

In disease treatment, the utilisation of medicinal plants has witnessed a discernible rise, driven by concerns over the adverse effects associated with synthetic drugs available in the market. Analyses of the plant Christia vespertilionis (L.f.) Bakh. F., indigenous to Malaysia, has suggested its antidiabetic property linked to α-glucosidase inhibition, but metabolites responsible for antidiabetic are unexplored. The metabolomics approaches and molecular docking simulations were integrated to identify the putative α-glucosidase inhibitors and their enzyme interaction. In this study, the crude leaves extracted from this plant were extracted using solvents of varying polarity, followed by gas and liquid chromatography coupled with mass spectrometry metabolomics. The highest inhibition activity in a mixture of n-hexane and ethyl acetate (1:1, v/v)) was observed. Six putative metabolites corresponding to antidiabetic activity were identified: palmitic acid (2), linolenic acid (4), 7-tetradecenal (5), aloeemodin-8-monoglucoside (14), bruceine I (15), and sanjidin B (16). The mechanism of action of all the identified compounds is competitive, mainly involving hydrophobic and hydrogen bonding interactions with the protein residues. Compounds 14, 15, and 16 exhibited strong binding capabilities with both enzyme crystal structures compared to the positive control, quercetin. The metabolites extracted from C. vespertilionis leaves have demonstrated promising antidiabetic effects. These antidiabetic compounds can potentially commercialise new drug candidates in managing diabetes conditions.

Synthesis, structural, biological applications, DFT, molecular docking studies on Fe(III), Co(II), and Ni(II) complexes incorporating 2‐(pyridin‐2‐yl)phenol and 1H‐benzimidazole‐2‐carboxylic acid

This study provides a detailed investigation into the synthesis, characterization, and biological activities of the coordination compounds FePPHBZC, CoPPHBZC, and NiPPHBZC. These compounds were synthesized with high yields by reacting chloride salts of Iron, Cobalt, or Nickel with 2‐(pyridin‐2‐yl)phenol (PPH) and 1H‐benzimidazole‐2‐carboxylic acid (BZC) in a 1:1:1 ratio. Various techniques including spectroscopic (IR, UV–vis, mass spectra), elemental analysis, conductivity, magnetic, and thermal analyses confirmed the formation and structure of these coordination compounds. Density functional theory (DFT) calculations were used to study their electronic structure, stability, and reactivity. 3D modeling revealed hexacoordinated geometries for Fe and Co complexes and a tetrahedral coordination for the Ni complex. Analysis of the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and other reactivity parameters indicated changes in reactivity upon metal coordination. Molecular Electrostatic Potential (MEP) diagrams identified electron‐rich areas prone to nucleophilic attack, important for protein interactions during docking studies. Biological evaluations demonstrated that metal–ligand complexes exhibit enhanced antimicrobial, antioxidant, and anti‐inflammatory activities compared to individual ligands, with larger inhibition zones and higher inhibitory activity. Molecular docking studies showed strong interactions between metal–ligand complexes and target proteins, suggesting potential therapeutic applications. Among them, FePPHBZC exhibited the strongest interactions, followed by CoPPHBZC and NiPPHBZC, characterized by hydrogen bonding, ionic interactions, and other non‐covalent interactions, contributing to their enhanced stability and binding affinity.