Superior Inhibitory Effect Research Articles

Combined transcriptome and metabolome analysis revealed the antimicrobial mechanism of Griseorhodin C against Methicillin-resistant Staphylococcus aureus

The global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.

2-(2-Phenylethyl)chromone dimers as melanin production inhibitors from agarwood of Gyrinops walla Gaertn

Agarwood is well known to be used and traded as luxurious perfume and cosmetic traditional medicine. Gyrinops walla Gaertn, a newly discovered source of agarwood, has garnered increasing attention. Modern pharmacological studies indicated that 2-(2-phenylethyl)chromones are one of the main chemical constituents in agarwood, known for their diverse biological activities. With the aim to study the cosmetic function of 2-(2-phenylethyl)chromones, phytochemical study on the agarwood from G. walla was carried out, and led to the identification of ten new 2-(2-phenylethyl)chromone dimers. All the structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS, as well as ECD calculation. Biological activity showed that all the compounds showed the tyrosinase inhibitory activity with IC50 values ranging from 17.70 ± 1.47–140.30 ± 6.43 μM (kojic acid as the positive control with IC50 value of 24.68 ± 0.30 μM). The kinetic studies presented that compounds 8-10 were competitive inhibitors for tyrosinase, and molecular docking simulations revealed the binding sites and interactions of compounds 3, 4, and 10. Moreover, all the isolated compounds showed a superior inhibitory effect on melanin production in B16 cells compared to kojic acid. Therefore, 2-(2-phenylethyl)chromones could be developed to be melanin production inhibitors used as cosmetic traditional medicine.

Repurposing TAK-285 as An Antibacterial Agent against Multidrug-Resistant Staphylococcus aureus by Targeting Cell Membrane.

Infections and antimicrobial resistance are becoming serious global public health crises. Multidrug-resistant Staphylococcus aureus (S. aureus) infections necessitate novel antimicrobial development. In this study, we demonstrated TAK-285, a novel dual HER2/EGFR inhibitor, exerted antibacterial activity against 17 clinical methicillin-resistant S. aureus (MRSA) and 15 methicillin sensitive S. aureus (MSSA) isolates in vitro, with a minimum inhibitory concentration (MIC) of 13.7μg/mL. At 1 × MIC, TAK-285 completely inhibited the growth of S. aureus bacterial planktonic cells, and at 2 × MIC, it exhibited a superior inhibitory effect on intracellular S. aureus SA113-GFP compared to linezolid. Moreover, TAK-285 effectively inhibited biofilm formation at sub-MIC, eradicated mature biofilm and eliminated bacteria within biofilms, as confirmed by CLSM. Furthermore, the disruption of cell membrane permeability and potential was found by TAK-285 on S. aureus, suggesting its targeting of cell membrane integrity. Global proteomic analysis demonstrated that TAK-285 disturbed the metabolic processes of S. aureus, interfered with biofilm-related gene expression, and disrupted membrane-associated proteins. Conclusively, we repurposed TAK-285 as an antimicrobial with anti-biofilm properties against S. aureus by targeting cell membrane. This study provided strong evidence for the potential of TAK-285 as a promising antimicrobial agent against S. aureus.

Yeast Synthesis and Herbicidal Activity Evaluation of Aspterric Acid.

Aspterric acid (AA) is a novel natural product herbicide that targets dihydroxyacid dehydratase in plants. In this study, we introduced two distinct AA biosynthesis-related gene clusters into Saccharomyces cerevisiae and screened the core biosynthetic enzyme, sesquiterpene cyclase, from various fungi. The combination of sesquiterpene cyclase from Aspergillus taichungensis IBT 19404 and two cytochrome P450s from Penicillium brasilianum resulted in the optimal AA synthesis efficiency in yeast, with the highest titer of 33.21 mg/L achieved by optimizing fermentation conditions in shake flasks. Moreover, the herbicidal effects of AA on weed germination and growth were evaluated. Notably, AA strongly inhibited the germination of Amaranthus tricolor, Portulaca oleracea, Bidens pilosa, Lolium perenne, and Leptochloa chinensis. Furthermore, AA could also inhibit the shoot and root growth of weeds with a superior inhibitory effect on roots relative to shoots. Our work not only provides a sustainable method for the biosynthesis of AA in yeast but also paves the way for the application of AA as a preemergence herbicide.

Color fastness and antimicrobial activity of Gardenia jasminoides extract against antimicrobial-resistant Staphylococcus aureus

This study investigated the antimicrobial efficacies of fabrics (100% cotton and 100% silk) dyed with an ethanol extract of Gardenia jasminoides (G. jasminoides). More specifically, these fabrics were dyed using a G. jasminoides extract with a dye bath ratio of 1:20 at 40–60 °C for 60 min, followed by post-mordanting. The concentrations of the aluminum sulfate, copper sulfate, and ferrous sulfate mordants were each set to 3% (o.w.f.). The samples were mordanted using a mordant bath ratio of 1:30 at 40 °C for 20 min. The iron mordant slightly increased the dye uptake (K/S) of the cotton fabric but did not increase the dye uptake (K/S) of the silk fabric. The antimicrobial efficacies of the dyed fabrics against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 33591 were determined to be 99.8 and 87.8% for the cotton and silk fabrics, respectively. The inhibitory effects of the cotton and silk fabrics against MRSA were 30.5 × and 167.3 × the inoculum size, respectively, indicating the superior inhibitory effect of the dyed cotton fabric. These results suggest that the fabrics dyed with G. jasminoides extract may possess antibacterial activity against antimicrobial-resistant bacteria.

Design, synthesis and biological evaluation of novel TMPRSS2-PROTACs with florosubstituted 4-guanidino-N-phenylbenzamide derivative ligands

Transmembrane Serine Protease 2 (TMPRSS2) plays a critical role in tumorigenesis and progression, making its degradation a promising therapeutic strategy. In this study, we designed and synthesized TMPRSS2-PROTACs, including VPOT64 and VPOT76, based on camostat. Both compounds exhibited superior inhibitory effects on HT-29 colorectal and Calu-3 lung cancer cells compared to paclitaxel. Notably, VPOT76 effectively degraded TMPRSS2, significantly inhibiting the proliferation of TMPRSS2-positive HT-29 cells and inducing apoptosis with an IC50 of 0.39 ± 0.01 μM. Flow cytometry analysis demonstrated that VPOT76 increased early apoptotic cells in a dose-dependent manner and caused G2 phase arrest at 0.8 μM. Colony formation assays showed that VPOT76 inhibited HT-29 colony formation, even at low concentrations, further confirming its anti-proliferative effect. Additionally, wound healing assays indicated that VPOT76 reduced the migration of HT-29 cells after 48 h, suggesting its potential to impair tumor cell invasion and metastasis. These findings highlight the multifaceted anticancer activities of VPOT76, including apoptosis induction, cell cycle arrest, colony formation inhibition, and migration suppression. Overall, this study establishes VPOT76 as a potent TMPRSS2-degrading PROTAC with strong therapeutic potential, laying the groundwork for further development of TMPRSS2-targeting treatments for colorectal and other cancers.

Targeted delivery of rhein via hyaluronic acid modified liposomes for suppression of growth and metastasis of breast cancer

Targeting and suppressing the malignant growth and metastasis of breast cancer has been challenging for years. Herein, a nanocarrier based on hyaluronic acid (HA)-modified cationic liposomes was developed for targeted delivery of rhein to achieve breast cancer therapy. The optimum HA-Lip-rhein had spherical and core-shell-like morphologies with an appropriate size of 189.7 ± 5.2 nm. Moreover, the HA-Lip-rhein exhibited higher cellular uptake in 4 T1 cells and enhanced cytotoxicity compared with unmodified liposomal rhein. Furthermore, in vitro cell migration and invasion inhibition assays showed that the HA-Lip-rhein exhibited superior inhibitory effects on breast cancer metastasis. HA-Lip-rhein improved the tumor targeting ability, anti-breast cancer activity, with good safety profile in the 4 T1 breast cancer-bearing mice compared with free rhein and Lip-rhein. The appearance of metastatic tumor nodules in the lungs and H&E staining of liver and lung organs confirmed that HA-Lip-rhein exerted strong antitumor efficacy and inhibited distant metastasis of breast cancer. Overall, the developed HA-Lip-rhein exhibited a good antitumor effect and suppression effect of distant metastasis, making it a novel and promising nanoplatform for further development.

Targeting Leishmaniasis with Nitrovinyl Derivatives: Their Synthesis, In Vitro Assessment, and Computational Exploration.

Leishmaniasis is an affliction caused by the protozoan parasites of the Leishmania genus. This disease impacts a substantial global populace, exceeding one million individuals, leading to disability-adjusted life years and fatalities, particularly within tropical regions. At present, the existing drug therapies have not attained a degree of efficacy that can be unequivocally classified as genuinely triumphant. In this context, the conception of novel compounds possessing the capacity to impede the parasite's life cycle at various stages holds considerable significance. In this research endeavor, an exploration was undertaken involving the design and synthesis of nineteen derivatives incorporating the nitrovinyl pharmacophore. The subsequent evaluation of their impacts on L. major was conducted through a combination of in vitro (amastigote and promastigote inhibition) and in silico (molecular docking) investigations. All of the compounds were synthesized and purified with good yields. In the amastigote inhibition assay, compounds 10, 15, and 18 showed better inhibitory effects than the standard drug meglumine antimonate (MA). Regarding the synergistic impact of synthesized compounds and MA together, all outcomes were significantly better than those of monotherapy of each in amastigote and macrophage forms. In the promastigote assay, compounds 2, 8, 12, 15, 16, 17, and 19 demonstrated superior inhibitory effects compared to MA. Moreover, compounds 4, 12, and 15 showed the best synergies with MA in inhibiting amastigotes. According to docking scores, 1XTP (a SAM-dependent methyltransferase) and 4G5D (Prostaglandin F synthase) receptors were found to be the most probable targets in their mechanism of action. In vitro evaluations and computational analyses strongly suggest that these compounds could be effective against both L. major amastigotes and promastigotes. Additionally, they exhibited notable synergistic interactions with MA against both living forms of the parasite.

Synthesis and biological evaluation of novel isobenzofuran-1(3H)-one derivatives as antidepressant agents

A series of novel isobenzofuran-1(3H)-one derivatives were designed and synthesized as antidepressants. Firstly, the serotonin reuptake inhibition of these compounds was tested in vitro, and most of them exhibited activity. Particularly, compounds 9d, 10a, and 10c demonstrated superior inhibitory effects and possibly avoided addiction via the μ-opioid receptor and CCK-B receptor. Secondly, the antidepressant effect of compound 10a was evaluated using chronic restraint stress (CRS)-induced mice. The results showed that compound 10a significantly improved CRS-induced depression-like behavior by increasing the neurotransmitters 5-HT in the cortex and THP2 expression in the hippocampus. Thirdly, compound 10a was further investigated and found to enhance CRS-induced hippocampal neuron damage recovery and elevate the expression of synaptic-associated proteins such as BDNF, TrkB, PSD95, and Spinophilin in CRS-induced mice. These findings suggested that novel isobenzofuran-1(3H)-one derivative showed efficacy in treating depression, with compound 10a emerging as a potential lead compound warranting further investigation.

<i>In vitro</i> studies on the development of microbial consortia for the management of major diseases in coconut and citrus

Microbial consortia for disease suppression involve combining multiple beneficial microorganisms to enhance their effectiveness in plant disease management. In present study, development of microbial consortia for the management of major diseases in coconut and citrus was carried out using bacteria Pseudomonas fluorescens, Pseudomonas putida (striata), Bacillus subtilis and fungi – Trichoderma reesei, T. harzianum, T. asperellum against major pathogens viz. Ganoderma lucidum, Thielaviopsis paradoxa, Phytopthora palmivora, Lasiodiplodia theobromae isolated from the coconut rhizosphere, and Fusarium solani isolated from the citrus rhizosphere. The promising fungal and bacterial antagonists were identified and studied for compatibility. Non-volatile compounds of consortia inhibited the test pathogens with an increase in concentration from 10 % to 75% with fungal consortia and bacterial consortia and also with mixed consortia which is composed of bacterial consortia + fungal consortia. Superior growth suppression was recorded with mixed consortia even at 10% concentration (59.44% to 65.83%) against the test pathogens in the ascending order of L. theobromae (59.44%) T. paradoxa (63.89%), G. lucidum (65.83%), P. palmivora (63.61%) and F. solani (62.78%). A similar trend was observed in 75% concentration where inhibition observed in the order of Thielaviopsis paradoxa (90.28%), G. lucidum (89.44%), F. solani (82.50%), L. theobromae (81.94%) and P. palmivora (81.39%). Volatile effect by bacterial consortia recorded the superior inhibition on test pathogens in the order of Ganoderma (85.28%), F. solani (75.28%), T. paradoxa (71.94%), P. palmivora (71.67%) and L. theobrome (67.50%) compared to the individual bioagents. Similarly, the fungal consortia showed the superior inhibitory effect on test pathogens in the order of G. lucidum (83.25%), P. palmivora (82.50%), L. theobromae (83.06%), F. solani (80.56%) and T. paradoxa (73.61%). Since there was no zone of inhibition between the strains, the interactions between Pseudomonas and Bacillus strains of Trichoderma spp. were compatible with one another. Neem cake recorded superior CFU population from 9.43 X 106 CFU at seven days by T. asperellum. Shelf life study on mixed consortia with bacterial + fungal bioagents in talc formulation indicated that all the bacterial and fungal CFU count recorded in 106 dilution for 90 days.

Identification of novel anti-leishmanials targeting glutathione synthetase of the parasite: a drug repurposing approach.

Drug repurposing has emerged as an effective strategy against infectious diseases such as visceral leishmaniasis. Here, we evaluated four FDA-approved drugs-valrubicin, ciclesonide, deflazacort, and telithromycin-for their anti-leishmanial activity on Leishmania donovani parasites, especially their ability to target the enzyme glutathione synthetase (LdGS), which enables parasite survival under oxidative stress in host macrophages. Valrubicin and ciclesonide exhibited superior inhibitory effects compared to deflazacort and telithromycin, inhibiting the promastigotes at very low concentrations, with IC50 values of 1.09 ± 0.09 μm and 2.09 ± 0.09 μm, respectively. Subsequent testing on amastigotes revealed the IC50 values of 1.74 ± 0.05 μm and 3.32 ± 0.21 μm for valrubicin and ciclesonide, respectively. Molecular and cellular level analysis further elucidated the mechanisms underlying the anti-leishmanial activity of valrubicin and ciclesonide.

Nickel(II) complex anchoring on anatase nanoparticles: A multifunctional approach to anticancer, anti-inflammatory, and antioxidant activities

In this study, a biologically active nickel(II) complex, [Ni(bipy)3]Cl2 (where bipy = 2,2′-bipyridine), was synthesized using a straightforward precipitation method. This nickel(II) complex was subsequently grafted onto anatase (TiO2) nanoparticles (NPs) through an adsorption technique, yielding nickel(II)-complex-grafted anatase (Ni-TiO2) NPs. The Ni-TiO2 NPs were thoroughly characterized using a range of analytical methods, including X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, UV–visible spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDAX), which confirmed the successful grafting of the complex onto the TiO2 NPs and maintained the structural integrity of the composite. The anticancer activity of the Ni-TiO2 NPs was assessed on Non-Small Cell Lung Cancer (NSCLC) cell lines using the MTT assay, revealing a significant enhancement in anticancer efficacy, with a 69 % improvement in cell inhibition compared to untreated cells. Moreover, the antioxidant potential of the Ni-TiO2 NPs was evaluated using the 1-Diphenyl-2-picrylhydrazyl (DPPH) assay, and their anti-inflammatory activity was determined through the protein denaturation assay. Both assays demonstrated that the Ni-TiO2 NPs exhibited superior inhibitory effects compared to the precursor Ni(II) complex, indicating enhanced bioactivity.

Azolato-Bridged Dinuclear Platinum(II) Complexes Exhibit Androgen Receptor-Mediated Anti-Prostate Cancer Activity.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Electrochemical Oxidative Functionalization of Pyrazolin‐5‐ones: Access to 4‐Quinoxalinone‐Substituted Pyrazoles

A strategy for the preparation of 4‐quinoxalinone‐substituted pyrazole derivatives by electrochemical functionalization of pyrazolin‐5‐ones is reported. Quinoxalinones, possessing significant biological activities, serve as aryl sources and participate in the transformation under electrochemical conditions without the necessity of adding extra oxidants and catalysts. This method features one‐pot synthesis, scale‐up and late‐stage functionalization of bioactive molecule derivatives. Notably, activity testing reveals that some compounds exhibit superior inhibitory effects on the proliferation of A549 cells compared to 5‐fluorouracil.

Integrating Blood Biomarkers and Marine Brown Algae-Derived Inhibitors in Parkinson's Disease: A Multi-scale Approach from Interactomics to Quantum Mechanics.

Parkinson's disease (PD) involves alpha-synuclein accumulation according to Braak's pattern, with diverse clinical progressions that complicate diagnosis and treatment. We aimed to correlate Braak's pattern with rapid progressive PD to identify blood-based biomarkers and therapeutic targets exploiting brown algae-derived bioactives for potential treatment. We implemented a systematic workflow of transcriptomic profiling, co-expression networks, cluster profiling, transcriptional regulator identification, molecular docking, quantum calculations, and dynamic simulations. The transcriptomic analyses exhibited highly expressed genes at each Braak's stage and in rapidly progressive PD. Co-expression networks for Braak's stages were built, and the top five clusters from each stage displayed significant overlap with differentially expressed genes in rapidly progressive PD, indicating shared biomarkers between the blood and the PD brain. Further investigation showed, NF-kappa-B p105 as the master transcriptional regulator of these biomarkers. Molecular docking screened phlorethopentafuhalol-A from brown algae, exhibiting a superior inhibitory effect with p105 (- 7.51kcal/mol) by outperforming PD drugs and anti-inflammatory compounds (- 5.73 to - 4.38kcal/mol). Quantum mechanics and molecular mechanics (QM/MM) calculations and dynamic simulations have confirmed the interactive stability of phlorethopentafuhalol-A with p105. Overall, our combined computational study shows that phlorethopentafuhalol-A derived from brown algae, may have healing properties that could help treat PD.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

Inhibition of SARS-CoV-2 Replication by Self-Assembled siRNA Nanoparticles Targeting Multiple Highly Conserved Viral Sequences.

Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Phytoecdysteroids from Dioscorea dumetorum (Kunth) Pax. and their antioxidant and antidiabetic activities

Diabetes is a significant global health challenge, affecting circa 540 million adults worldwide. Dioscorea dumetorum, a Nigerian folkloric antidiabetic plant is severely understudied in terms of its bioactive phytochemical constituents. Antidiabetic guided isolation of the tubers and peels of D. dumetorum afforded three phytoecdysteroids bearing a cis-fused A/B ring junction including two new ones: 24-hydroxymuristerone A (1) and 24-hydroxykaladasterone (2), alongside the known muristerone A (3). Additionally, 2,2′,7,7′-tetramethoxy-[1,1′-biphenanthrene]-4,4′,6,6′-tetraol (4), batatasin I (5), and dihydroresveratrol (6) were isolated. Structural elucidation relied on spectroscopic, spectrometric methods, and comparison with existing literature. The ethyl acetate extracts of both the tubers and peels of D. dumetorum exhibited the highest phenolic content, correlating with potent antioxidant activity. Compounds 4 (IC50 = 0.10 mg/mL) and 6 (IC50 = 0.22 mg/mL) demonstrated superior inhibitory effects against α-glucosidase compared to acarbose (IC50 = 0.63 mg/mL). In contrast, compounds 3, 4, and 5 showed reduced α-amylase inhibition, with IC50 values of 2.58, 3.78, and 1.12 mg/mL, respectively, compared to acarbose (IC50 = 0.42 mg/mL). These observed bioactivities validate the traditional use of D. dumetorum and contribute valuable phytochemical data to the scientific literature of the species.

Antagonistic activity of biocontrol agent Trichoderma spp. against Fusarium sp., the causal agent of Ananas comosus fruitlet rot

Pineapple (Ananas comosus) is a significant crop, with an annual production exceeding 25 million tons. However, fusariosis can severely impact its cultivation, a fungal disease that causes fruitlet rot and results in substantial yield losses. To decrease dependency on chemical control methods, biocontrol agents (BCAs) present a promising alternative. Among these, Trichoderma species are noteworthy due to their diverse antagonistic mechanisms. The efficacy of each mechanism can be assessed through fungal confrontation assays. This study aimed to isolate, identify, and evaluate in-vitro nine Trichoderma spp. strains as potential BCAs against Fusarium sp. associated with pineapple fruitlet rot. The antagonistic fungi were isolated from rhizosphere soils in both open-field and greenhouse pineapple farms in Misiones province, Argentina. Identification of the fungi required both morphologic and genetic data. In the in-vitro assays, the capabilities for direct competition for substratum, production of metabolites, and mycoparasitism were evaluated. The results indicated that isolates T. harzianum TC7, T. harzianum TC9, T. asperellum TU3, and T. asperellum TU4 had statistically superior inhibitory effects against Fusarium sp. These isolates can be potentially used in formulating natural fungicides to reduce pineapple fruitlet rot caused by Fusarium, promoting sustainable production practices. Keywords: pineapple, confrontation, mycoparasitism, metabolites, ITS region