Excellent Activity Research Articles

Synergistic combination of Mn/Fe bimetal-doped carbon nitride and peroxymonosulfate for efficient photocatalytic degradation of antibiotics

The widespread of antibiotics has resulted in potential threats to the aquatic environment and human health. The visible light-assisted peroxymonosulfate (PMS) activation method is considered to be an effective way to remove antibiotics in wastewater. In this study, Mn/Fe bimetal doped graphitic carbon nitride (MnFe-CN-x) was first synthesized for PMS activation under visible light towards tetracycline (TC) removal. The optimized MnFe-CN-50 possessed the excellent photocatalytic activity, PMS activation performance and photo-Fenton-like synergistic effect. In the photo-Fenton-like system, TC (20mgL-1) was degraded by 99% in 50min and the kinetic constant was 0.074min-1. The high dispersion of Mn and Fe in carbon nitride inhibited the recombination of charge carriers in MnFe-CN-x, increased its photocurrent density and charge mobility, effectively optimized the electronic structure, and promoted the generation of 1O2. Based on the analytical results of predictive toxicity evaluation software (TEST), it was confirmed that MnFe-CN-x could effectively reduce the environmental risks associated with antibiotic contamination. This study provided new insights into synthesizing bimetal-doped graphitic carbon nitride and the use of synergistic effects of photocatalysis and PMS activation to remove organic pollutants from wastewater.

In-situ formed stable Pt nanoclusters on ceria-zirconia solid solutions induced by hydrothermal aging for efficient low-temperature CO oxidation

Pt nanoclusters (PtC) on the surface of ceria-zirconia solid solutions exhibit superior low-temperature CO oxidation activity compared to Pt single atoms (Pt1). However, the redispersion behavior of the PtC to Pt1 lowers the efficiency of CO Oxidation. In this work, the stable surface hydroxyl groups were constructed by high-temperature hydrothermal aging treatment. Specifically, the Pt1 catalyst (Pt/CZOe-SA) prepared by atom trapping was subjected to high-temperature hydrothermal treatment to obtain the stable PtC catalyst (Pt/CZOe-HT) with in-situ formed PtC. The experimental results showed that PtC with 2–3 nm size could achieve excellent low-temperature activity and thermal stability. In addition, the ab initio molecular dynamics and density functional theory calculations revealed the specific evolution process of dynamic dispersion for PtC with or without hydroxyl groups from the femtosecond scale, suggesting that the hydroxyl groups limited the dispersion of PtC in the form of “energy fence”. The hydrothermal treatment not only introduced high-temperature stable hydroxyl groups to improve the stability of the in-situ formed PtC, but also optimized the ratio of Pt1 and PtC, and then enhanced the low-temperature activity by the synergistic effect between Pt1 and PtC. The present work can provide theoretical guidance for developing high-performance and high-stability Pt-based catalysts.

Green synthesis of chitosan nanoparticles using Cassia fistula leaf extract: evaluation of antimicrobial, antioxidant, antibiofilm, and cytotoxic activities.

The emerging field of green synthesis within nanobiotechnology presents significant environmental and economic advantages compared to conventional methodologies. This study investigates the synthesis and application of chitosan nanoparticles (ChNPs) using Cassia fistula (CF) leaf extract as a sustainable, and bio-based approach. Characterization of CF-ChNPs confirmed effective bioconversion and also demonstrated significant antimicrobial activity. Notably, CF-ChNPs demonstrated a remarkable antimicrobial effect against Pseudomonas aeruginosa, with a zone of inhibition of 17 ± 0.2mm surpassing the impact on other organisms tested. The CF-ChNPs exhibited an initial burst release of 28 ± 0.28% after 2h, gradually achieving a controlled release of 76.3 ± 0.43% within 24h. In addition, CF-ChNPs exhibited an antioxidant activity of 43.1 ± 0.48% and showed excellent antibiofilm activity against Staphylococcus aureus in comparison to other organisms. The cell viability assay results have confirmed that CF-ChNPs do not have any negative impact on the viability of L929 fibroblasts, further highlighting their potential as versatile nanomaterials for treating microbial infections and other therapeutic applications.

Plasma synthesis of Pt/C catalysts and their electrocatalytic performance

Abstract A simple, green, and scalable approach, utilizing dielectric barrier discharge (DBD) plasma in lieu of chemical reductants, is presented for producing Pt/C catalysts. The results revealed crystalline well-dispersed Pt nanoparticles of small sizes were generated on the surface of carbon support, where the Pt loading can be regulated by adjusting the H2PtCl6 concentration. The resulting Pt/C catalysts demonstrated excellent catalytic activity in both acidic and alkaline electrolytes for hydrogen evolution reactions (HER) and methanol oxidation reactions (MOR). With the rise of the Pt loading, the catalytic activity gradually improves. Specifically, for HER, an overpotential value of 120 mV was measured for the 8 wt% Pt/C-modified electrode at a geometric current density of −10 mA cm−2, with a Tafel slope of 45.4 mV dec−1 in acidic electrolyte. The values became 208 mV and 83.7 mV dec−1 in alkaline electrolyte. Same phenomenon was also observed in MOR, where the increase of the Pt loading results in faster electron transport rate and stronger methanol oxidation peak. Besides, the catalytic activity of the plasma-prepared Pt/C catalysts is better than the commercial samples with the same Pt loading. This work demonstrates a DBD plasma-assisted strategy for the preparation of Pt/C catalysts in an efficient and environmentally friendly manner.

Design and Synthesis of 3-Carene-Derived Amide-Thiourea/Nanochitosan Complexes with Excellent Laccase Inhibitory Activity and Sustained Releasing Performance for Crop Protection

Design and Synthesis of 3-Carene-Derived Amide-Thiourea/Nanochitosan Complexes with Excellent Laccase Inhibitory Activity and Sustained Releasing Performance for Crop Protection

A multifunctional composite scaffold responds to microenvironment and guides osteogenesis for the repair of infected bone defects

Treating bone defect concomitant with microbial infection poses a formidable clinical challenge. Addressing this dilemma necessitates the implementation of biomaterials exhibiting dual capabilities in anti-bacteria and bone regeneration. Of particular significance is the altered microenvironment observed in infected bones, characterized by acidity, inflammation, and an abundance of reactive oxygen species (ROS). These conditions, while challenging, present an opportunity for therapeutic intervention in the context of contaminated bone defects. In this study, we developed an oriented composite scaffold containing copper-coated manganese dioxide (MnO2) nanoparticles loaded with parathyroid hormone (PMPC/Gelatin). The characteristics of these scaffolds were meticulously evaluated and confirmed the high sensitivity to H+, responsive drug release and ROS elimination. In vitro antibacterial analysis underscored the remarkable ability of PMPC/Gelatin scaffolds to substantially suppressed bacterial proliferation and colony formation. Furthermore, this nontoxic material demonstrated efficacy in mitigating ROS levels, thereby fostering osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing angiogenic ability. Subsequently, the infected models of bone defects in rat skulls were established to investigate the effects of composite scaffolds on anti-bacteria and bone formation in vivo. The PMPC/Gelatin treatment exhibited excellent antibacterial activity, coupled with enhanced vascularization and osteogenesis at the defect sites. These compelling findings affirm that the PMPC/Gelatin composite scaffold represents a promising avenue for anti-bacteria and bone regeneration.

Nano‐High Entropy Materials in Electrocatalysis

AbstractHigh entropy materials (HEMs) compositing of at least five elements have gained widespread attention in the field of electrocatalysis due to their tunable activities and high stability. These intrinsic properties can be further highlighted when the size of HEMs comes to the nanoscale. In nanostructured HEMs, the fascinating properties including large composition space, multi‐element synergy, and high configuration entropy are expected to endow nano‐HEMs with excellent catalytic activity and stability, thus providing greater potential for the design of advanced electrocatalysts. In this review, nano‐HEMs are differentiated in detail in dimensions and the common synthesis methods are summarized. Additionally, from the perspective of the complex nanostructure‐performance relationship, the applications of nano‐HEMs in electrocatalysis systems, including water‐splitting (hydrogen evolution reaction (HER), oxygen evolution reaction (OER)), hydrogen oxidation reaction (HOR), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO2RR), nitrogen reduction reaction (NRR) and alcohol oxidation reaction (AOR) are discussed. Finally, the main challenges faced by nano‐HEMs electrocatalysis are underscored. This review is expected to provide more insights into understanding and developing efficient electrocatalytic materials for practical applications.

Two-dimensional Janus MXTe (M = Hf, Zr; X = S, Se) piezoelectrocatalysts: a comprehensive investigation of its electronic, synthesis feasibility, electric polarization, and hydrogen evolution reaction activity

Abstract We computationally investigated potential piezoelectrocatalysts, two-dimensional (2D) Janus MXTe (M = Hf, Zr; X = S, Se). The structural and electronic properties, synthesis feasibility, piezoelectric properties, and hydrogen evolution reaction were calculated. Our results showed that these 2D Janus MXTe are narrow-gap semiconductors, indicating great conductivity for electrocatalysis. The feasibility of synthesis was comparable to the already synthesized Janus materials. To exhibit a piezoelectrocatalytic effect, the material has to be piezoelectric and catalytically effective simultaneously. As the Janus structure breaks the centrosymmetry, the considered MXTe are intrinsically piezoelectric. We therefore calculated the dipole moments and the variation of out-of-plane polarization upon strain. The computed piezoelectric coefficient e 31 is within the same order of magnitude as that of other Janus 2D materials. Finally, although pristine 2D Janus MXTe were inert to hydrogen evolution reaction, incorporation of single-atom defects was found to boost hydrogen adsorption significantly. The catalytic efficacy can be further tuned by biaxial tensile strain, effectively controlling the Gibbs free energy of adsorption to be close to the thermoneutral value that is indicative of an excellent hydrogen evolution reaction activity, at least for ZrSTe Janus monolayer. In summary, this work proposed and comprehensively investigated a new class of possible piezoelectrocatalysts, 2D Janus materials, which is feasible to be synthesized, catalytically effective, and has great conductivity.

Encapsulation of Ru nanoparticles within NaY zeolite for ammonia decomposition

Uniform and minuscule Ru particles confined in NaY zeolite (Ru@NaY) are prepared via a simple in situ synthesis technique. Transmission electron microscopy studies indicate that the Ru particles are encapsulated within the micropores of NaY zeolite and form a uniform size of 1.5–3.5 nm. Thanks to the effective confinement of Ru particles within the NaY zeolite, as well as the high concentration of B-5 sites and basic sites, the prepared Ru@NaY catalysts show excellent NH3 decomposition activity and highly efficient H2 formation. Notably, the 0.1Ru@NaY catalyst achieves a 92.7% NH3 conversion and a H2 formation rate of 690 mmol min−1·gRu−1 at 500 °C and GHSV = 9000 mLNH3·gcat−1·h−1 and shows outstanding stability throughout a 95-h lifetime test. The encapsulation synthesis of Ru clusters in zeolites endows the catalysts with exceptional catalytic activities and excellent stability, thus providing new prospects for the production of H2 from NH3 decomposition.

Iron nanoparticle engineered N-doped graphitic carbon composite as a binary electrocatalyst for overall water splitting and supercapacitor

In this study, we report on the tailored synthesis of nitrogen-(N)-doped carbon and iron-(Fe)-loaded N-doped carbon composites and their use for the oxygen evolution reaction (OER), hydrogen evolution reaction (HER), overall electrochemical water splitting, and supercapacitors. FE-SEM and HR-TEM analyses reveal that the developed composite material exhibits a core-shell structure with enhanced porosity upon Fe incorporation. By adjusting the ratio of Fe to N-doped carbon in the composites, it was identified that the catalyst 5Fe@NC demonstrates outstanding electrochemical activity alongside commendable stability. Specifically, the 5Fe@NC electrocatalyst achieves current densities of +10 mAcm−2 and -10 mAcm−2 in alkaline electrolyte with minimal overpotentials of 376 mV and 520 mV, respectively. Notably, impressive Tafel slopes of 84 mV/dec and 212 mV/dec for the OER and HER were obtained, indicating superior kinetic activity of the developed composite materials. As a supercapacitor, 5Fe@NC electrode material exhibits a measurable specific capacitance of 294 F/g at 0.5 A/g current density with excellent durability (78 % retention after 1000 charge-discharge cycles). Furthermore, we conducted assessments on stability, charge transfer resistance, and ECSA, yielding excellent outcomes. This work successfully demonstrates a highly effective dual-purpose electrocatalyst prepared from indole and furfural (heterocycles abundant in biomass), exhibiting excellent electrochemical activity and stability in facilitating HER and OER within alkaline electrolytes.

Charge Transfer in n-FeO and p-α-Fe2O3 Nanoparticles for Efficient Hydrogen and Oxygen Evolution Reaction

This study aims to explore the n-FeO and p-α-Fe2O3 semiconductor nanoparticles in hydrogen (HER) and oxygen (OER) evolution reactions and a combined full cell electrocatalyst system to electrolyze the water. We have observed a distinct electrocatalytic performance for both HER and OER by tuning the interplay between iron oxidation states Fe2+ and Fe3+ and utilizing phase-transformed iron oxide nanoparticles (NPs). The Fe2+ rich n-FeO NPs exhibited superior HER performance compared to p-α-Fe2O3 and Fe(OH)x NPs, which is attributed to the enhancement in n-type semiconducting nature under HER potential, facilitating the electron transfer for the reduction in H+ ions. In contrast, p-α-Fe2O3 NPs demonstrated excellent OER activity. An H-cell constructed using n-FeO||p-α-Fe2O3 NPs as cathode and anode achieved a cell voltage of 1.87 V at a current density of 50 mA/cm2. The cell exhibited remarkable stability after 30 h of activation and maintained the high current density of 100 mA/cm2 for 80 h with a negligible increase in cell voltage. This work highlights the semiconducting properties of n-FeO and p-α-Fe2O3 for the electrochemical water splitting system using the band bending phenomenon under the applied potential.

Recent advancement of novel marine fungi derived secondary metabolite fibrinolytic compound FGFC in biomedical applications: a review

For several decades, products derived from marine natural sources (PMN) have been widely identified for several therapeutic applications due to their rich sources of bioactive sub-stances, unique chemical diversity, biocompatibility and excellent biological activity. For the past 15 years, our research team explored several PMNs, especially fungi fibrinolytic compounds (FGFCs). FGFC is an isoindolone alkaloid derived from marine fungi, also known as staplabin analogs or Stachybotrys microspora triprenyl phenol (SMTP). For instance, our previous studies explored different types of FGFCs such as FGFC 1, 2, 3 and 4 from the marine fungi Stachybotrys longispora FG216 derived metabolites. The derivatives of FGFC are potentially employed in several disease treatments, mainly for stroke, cancer, ischemia, acute kidney injury, inflammation, cerebral infarction, thrombolysis and hemorrhagic activities, etc. Due to the increasing use of FGFCs in pharmaceutical and biomedical applications, it is important to understand the fundamental signaling concept of FGFCs. Hence, for the first time, this review collectively summarizes the background, types, mode of action and biological applications of FGFCs and their current endeavors for future therapies.

Heterovalent State and Oxygen Vacancy Defect Structure‐Associated V/S Co‐Doped SnO2 for Catalytic Reduction of Organic and Cr6+ Pollutants in the Dark

AbstractV/S co‐doped SnO2 bimetal sulfur‐oxides catalysts labeled as (Sn,V)1‐x(S,O)2‐y or (SnVSO) with heterovalent state and oxygen vacancy defect are prepared via a green and facile method. The presence of SnVSO in the heterovalent states of Sn4+/Sn2+ and V5+/V4+ facilitates the rapid transfer of the electrons. It improves the electronic charge lifetime, accelerating the efficiency of the catalytic reduction of pollutants. The V/S co‐doped SnO2 regulates the bandgap energy structure. The hydrazine adjusts the heterovalent metal states to reduce Sn4+ to Sn2+ and V5+ to V4+. Also, it introduces oxygen vacancies to SnVSO to maintain the charge equilibrium and increase the active surface reactive sites, which enhance the catalytic activity. The SnVSO‐3 prepared with 0.4 mL hydrazine exhibits excellent catalytic activity, which wholly reduces 20 ppm of 100 mL methyl orange (MO), rhodamine B (RhB), methylene blue (MB), hexavalent chromium (Cr6+), and 4‐nitrophenol (4‐NP) within 6 min. In addition, the SnVSO‐3 also has good stability after repeated 6 runs with a reduction efficiency of 96.8%. Therefore, the V/S co‐doped SnO2 sulfur oxide catalysts have a promising potential for reducing Cr6+ and organic pollutants.

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Design, Synthesis, Anti-TMV Activity, and Structure-Activity Relationships of Seco-pregnane C21 Steroids and Their Derivatives.

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

Design and Synthesis of Novel Indole-Derived N-Methylcarbamoylguanidinyl Chitinase Inhibitors with Significantly Improved Insecticidal Activity.

Chitinases play an important role in the molting process of insects and are potential targets for the development of green insecticides. Based on the feature that the +1/+2 sites in OfChtI, OfChtII, and OfChi-h have tryptophan residues in mismatch-parallel position, a strategy to introduce indole scaffold into chitinase inhibitors was proposed, and multitarget chitinase inhibitors containing N-methylcarbamoylguanidinyl and indole scaffold were successfully synthesized. The inhibitory activity showed that compound 8u exhibited significant inhibitory activity against OfChtI, OfChtII, and OfChi-h, with IC50 values of 0.7, 0.79, and 0.58 μM, and Ki values of 0.05 ± 0.005, 0.065 ± 0.004, and 0.025 ± 0.006 μM, respectively. In vivo insecticidal activity showed that compounds 8a and 8g exhibited excellent insecticidal activity against Plutella xylostella and Mythimna separata, with LC50 values of 0.79 and 9.17 mg/L against P. xylostella, respectively, and 3.58 and 83.09 mg/L against M. separata, respectively, making them the most potent chitinase inhibitors with in vivo insecticidal activity discovered to date. The inhibition mechanism and binding free energy results suggested that N-methylcarbamoylguanidinyl binds to the -1 catalytic site, while additional interactions acquired by π-π stacking and hydrophobic interactions of the indole scaffold with tryptophan increase the binding affinity of the targets to chitinases. This work provides a new direction for the development of chitinase inhibitors with compounds 8a and 8g potentially serving as promising candidates for pesticide development.

Antibacterial activity and mechanism of Stevia extract against antibiotic-resistant Escherichia coli by interfering with the permeability of the cell wall and the membrane

Natural plant-derived compounds with broad-spectrum antimicrobial activity have become an effective strategy against multidrug-resistant bacteria. The present study was designed to compare the antibacterial activity of six chlorogenic acid (CA) isomers extracted from stevia and investigated the underlying antibacterial mechanisms involved. The results indicated that isochlorogenic acid C (ICAC) exhibited the strongest antibacterial activity against the tested bacteria, especially E. coli, at a 2 mg/mL minimum inhibitory concentration (MIC) and 8 mg/mL minimum bactericidal concentration (MBC). At the MBC, ICAC inhibited 72.66% of the clinical multidrug-resistant strains. Scanning electron microscopy (SEM) revealed that ICAC induced considerable morphological alterations in E. coli ATCC25922 and C4E2. The significant increase in the activity of extracellular alkaline phosphatase (AKP) indicated that ICAC damages the permeability of the bacterial cell wall. Additionally, the intracellular membrane (IM) permeability and the content of lipopolysaccharide (LPS), a main component of the outer membrane (OM), were determined. The significant decrease in LPS content and increased leakage of intracellular proteins and K+ from E. coli indicated that ICAC could induce the exfoliation of OM and disrupt IM permeability, resulting in the loss of barrier function. The uptake of propidium iodide (PI), a compromised cell membrane nucleic acid stain, and confocal laser scanning microscopy (CLSM) further demonstrated that ICAC disrupted IM integrity. Moreover, the bactericidal effect and damage to bacterial microstructural function occurred in a dose-dependent manner. These data demonstrate that ICAC has excellent antibacterial activity and is a promising approach for overcoming the antibiotic resistance of pathogenic bacteria.

Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

AbstractWe report here a Ni-NPs-catalyzed one-pot synthesis of 2-alkyl/aryl quinazolinone motifs via acceptorless dehydrogenation of alcohol, condensation of an aldehyde intermediate with 2-aminobenzamide, followed by a second dehydrogenation of the cyclized intermediate. The protocol is atom-economical and require earth-abundant Ni as the catalyst. The present report involves the annulation of 2-aminobenzamide with various types of primary alcohols, including aryl/heteroaryl methanol, and aliphatic alcohols, and produces high yields of the desired products under neat conditions. The catalyst was synthesized via a high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD, and ICP-MS. The catalyst is stable even in air at room temperature and displayed excellent activity in the acceptorless dehydrogenative coupling synthesis of quinazolinones and could be recycled five times without appreciable loss of its activity.

Design, synthesis, bioactivity and action mechanism of N-substituted N'-phenylpicolinohydrazides against phytopathogenic fungi.

N'-phenylpicolinohydrazide has been proven to be a promising lead compound for research and development of novel fungicides for agriculture in our previous study. As our continuing research, in this study, a series of N-substituted derivatives of N'-phenylpicolinohydrazide were synthesized and explored for the inhibition activity on nine phytopathogenic fungi and action mechanism. The results found that eleven of the compounds had excellent antifungal activity with more than 80% inhibition rates at 50 µg/mL on part or most of the fungi, especially A. solani and P. piricola. Compounds 5i, 5j and 5k showed EC50 values of < 8.0 µg/mL against A. solani superior to positive control carbendazim (EC50 = 36.0 µg/mL) while 5p and 5q exhibited the highest activity with EC50 values of 2.72 and 2.80 µg/mL against P. piricola superior to positive control boscalid (EC50>50.0 µg/mL). Furthermore, 5k also showed significant protective effect against A. solani infection on tomatoes in a concentration-dependent manner. Action mechanism research showed that 5k was able to increase the intracellular ROS level, change both MMP and permeability of cell membrane and damage mycelial morphology. Molecular docking studies showed that 5k could bind into ubiquinone-binding region of succinate dehydrogenase by hydrogen bonds, π-cation, π-π stacked, π-alkyl, and alkyl interactions. Additionally, the antibacterial activity was also investigated. Thus, N-substituted derivatives of N'-phenylpicolinohydrazide were emerged as novel and highly promising antifungal molecular skeletons to develop new fungicides for crop protection.

Design, Synthesis, Antifungal Evaluation, and Three-Dimensional Quantitative Structure-Activity Relationship of Novel 5-Sulfonyl-1,3,4-thiadiazole Flavonoids.

Plant pathogenic fungi frequently disrupt the normal physiological and biochemical functions of plants, leading to diseases, compromising plant health, and ultimately reducing crop yield. This study aimed to address this challenge by identifying antifungal agents with innovative structures and novel mechanisms of action. We designed and synthesized a series of flavonoid derivatives substituted with 5-sulfonyl-1,3,4-thiadiazole and evaluated their antifungal activity against five phytopathogenic fungi. Most flavonoid derivatives demonstrated excellent antifungal activity against Botrytis cinerea (B. cinerea), Alternaria solani (A. solani), Rhizoctorzia solani (R. solani), Fusarium graminearum (F. graminearum), and Colletotrichum orbiculare (C. orbiculare). Specifically, the EC50 values of 38 target compounds against R. solani were below 4 μg/mL, among which the compounds C13 (EC50 = 0.49 μg/mL), C15 (EC50 = 0.37 μg/mL), and C19 (EC50 = 0.37 μg/mL) had the most prominent antifungal activity, superior to that of the control drug carbendazim (EC50 = 0.52 μg/mL). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the cellular ultrastructures of R. solani mycelia and cells after treatment with the compound C19 revealed sprawling growth of hyphae, a distorted outline of their cell walls, and reduced mitochondrial numbers. Studying the 3D-QSAR between the molecular structure and antifungal activity of 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoid derivatives could significantly improve conventional drug molecular design pathways and facilitate the development of novel antifungal leads.