Facile Synthesis and First Antifungal Exploration of Tetracyclic Meroterpenoids: (+)-Aureol, (-)-Pelorol, and Its Analogs.

As an important bioactive molecular backbone, drimane meroterpenoids have drawn a great deal of attention from both pharmacologists and chemists. Inspired by the prevalidated success of conformational restriction in the discovery of novel pharmaceutical leads, two distinct tetracyclic drimane meroterpenoids, (-)-pelorol and (+)-aureol, were synthesized from the inexpensive starting material (-)-sclareol through 10 and 8 steps with 5.6% and 5.4% overall yield, respectively. The mild conditions, operational facility, and scalability enabled the expedient synthesis and biological exploration of not only natural products themselves but also their mimics. The first agrochemical exploration showed (-)-pelorol and (+)-aureol possessed good antifungal activity against Rhizoctonia solani, with EC50 values of 7.7 and 6.9 µM, respectively. This revealed that tetracyclic drimane meroterpenoids are valuable models for antifungal lead discovery.

Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.

Drimane meroterpenoids have drawn increasing attention in the discovery of novel pharmaceutical leads owing to their structural diversity and bioactivity variation, but further development is significantly impeded by the lack of an efficient modular route of preparation. A nickel-catalyzed decarboxylative cross-coupling paradigm has been established to expeditiously access a constellation of drimane meroterpenoids. The redox-active drimane precursor is a bench-stable coupling partner and is easily available from the inexpensive feedstock sclareol. This transformation features the tolerance of challenging functional groups (phenol, aldehyde, ester, etc.) and mild conditions with a low-cost nickel catalytic system. The synthetic utility is further highlighted by the direct scalable synthesis of challenging drimane meroterpenoids as diversifiable advanced intermediates for late-stage functionalizations. This method facilitated antifungal investigations and culminated in the discovery of compounds C8 and C3 as new antifungal leads against Rhizoctonia solani, with EC50 values of 4.9 and 7.2 µM, respectively.

The application of a novel hydrodynamic cavitation device to debride intra-articular monosodium urate crystals.

INTRODUCTION: Efficient and complete debridement of intra-articular deposits of monosodium urate crystals is rarely achieved by existing arthroscopic tools such as shavers or radiofrequency ablation, while cavitation technology represents a prospective solution for the non-invasive clearance of adhesions at intra-articular interfaces. METHODS: Simulation modeling was conducted to identify the optimal parameters for the device, including nozzle diameters and jet pressures. Gouty arthritis model was established in twelve rats that were equally and randomly allocated into a cavitation debridement group or a curette debridement group. A direct injection nozzle was designed and then applied on animal model to verify the effect of the cavitation jet device on the removal of crystal deposits. Image analysis was performed to evaluate the clearance efficiency of the cavitation device and the pathological features of surrounding tissue were collected in all groups. RESULTS: To maximize cavitation with the practical requirements of the operation, an experimental rig was applied, including a 1 mm direct injection nozzle with a jet pressure of 2.0 MPa at a distance of 20 mm and a nitrogen bottle as high-pressure gas source. With regards to feasibility of the device, the clearance rates in the cavitation group were over 97% and were significantly different from the control group. Pathological examination showed that the deposition of monosodium urate crystals was removed completely while preserving the normal structure of the collagen fibers. CONCLUSIONS: We developed a promising surgical device to efficiently remove intra-articular deposits of monosodium urate crystals. The feasibility and safety profile of the device were also verified in a rat model. Our findings provide a non-invasive method for the intraoperative treatment of refractory gouty arthritis.

Soil wind erosion evaluation and sustainable management of typical steppe in Inner Mongolia, China.

Soil wind erosion is an important ecological environmental problem that is widespread in arid and semi-arid regions. Currently, related studies are mainly focused on spatiotemporal characteristics or analysis of effector mechanisms, and they do not facilitate direct servicing of management decisions. In this paper, we used the Xilingol typical steppe in Inner Mongolia, China, as a study site to develop a decision framework for a comprehensive understanding of soil wind erosion and to promote sustainable management of steppes. In this study, we used the Revised Wind Erosion Equation model to simulate soil wind erosion. We combined this model with linear trend analysis to evaluate the ecological effects of soil wind erosion and wind erosion intensity, and delineated the gravity center migration path. We used the constraint line method to reveal the mechanisms by which climatic factors affected soil wind erosion, achieved the spatial visualization of wind-breaking and sand-fixing service flow, and proposed decision-based regional sustainable development suggestions. The results showed that long-term soil wind erosion will lead to soil coarsening and loss of soil nutrients. Soil wind erosion in the study site showed worsening trends and risks, and as such, ecological environment conservation and management are urgently required. The study framework promotes a clear understanding of the complex relationship of human-earth systems. The study results will aid in the ecological remediation of steppe landscapes and the prevention of desertification and will provide a foundation for win-win management of ecological conservation and economic development in arid and semi-arid regions.

Enantioselective total synthesis, divergent optimization and preliminary biological evaluation of (indole-N-alkyl)-diketopiperazines.

The first enantioselective total synthesis of the antifungal natural product (indole-N-isoprenyl)-tryptophan-valine diketopiperazine 5 was accomplished. Four stereoisomers of 5 were intentionally prepared, and the (R, R)-isomer is more favorable in enhancing the antifungal bioactivity. Divergent structural optimization of this attractive model was conducted from the chiral pool amino acids. Fine-tuning of the structure protruded the broad-spectrum antifungal 6b, which also showed good preventative efficacy against Sclerotinia scleotiorum. Compound 5d could accelerate both hypocotyl elongation and root growth of Eclipta prostrata even at the concentration of <2.5 ppm. This unique and easily accessible scaffold will be of prime importance in achieving agrochemical candidates with the novel scaffold.

Expediently Scalable Synthesis and Antifungal Exploration of (+)-Yahazunol and Related Meroterpenoids.

The efficient synthesis and antifungal exploration of (+)-yahazunol and related natural products are described. Central to this strategy is the Barton decarboxylative coupling, comprising a one-pot radical decarboxylation and quinone addition cascade. The scalable synthesis of (+)-yahazunol was accomplished in five longest linear sequences (LLS) starting from commercially available and inexpensive (-)-sclareol. The divergent translational potential of (+)-yahazunol was demonstrated by the expedient preparation of (-)-zonarone, (-)-isozonarone, (-)-zonarol, (-)-isozonarol, (+)-chromazonarol, and (+)-yahazunone. This approach also enables the formal synthesis of puupehenol, puupehedione, and hongoquercin A. Antifungal evaluation was performed, and this represents the first biological profiles for (+)-yahazunone, (+)-8- O-acetylyahazunone, and (+)-8- O-acetylyahazunol. (+)-Chromazonarol and (+)-yahazunone are promising candidates against Sclerotinia scleotiorum, with EC50 values of 24.1 and 28.7 µM, respectively, demonstrating advantages over the original model (DM) and synthesized heterocyclic mimic (3a) of meroterpenoids. This will favor the establishment of a chemical repertoire in the management of different plant diseases.

Pharmacological characteristics of the novel fungicide pyrisoxazole against Sclerotinia sclerotiorum.

Pyrisoxazole is a pyridine compound of demethylation inhibitor fungicides. In this study, baseline sensitivity of Sclerotinia sclerotiorum to pyrisoxazole was determined using 166 strains from the oilseed rape fields in 2014, 2015 and 2016. The EC50 values for mycelial growth inhibition ranged from 0.0214 to 0.5443 µg mL-1, with a mean EC50 value of 0.2329 ±â€¯0.1048 µg mL-1 and were normally distributed. The EC50 values had no significant difference among three populations from 2014, 2015, and 2016. There was no correlation with sensitivity between pyrisoxazole and carbendazim or iprodione. After treated with pyrisoxazole, we observed increased cell membrane permeability, and decreased exopolysaccharide and oxalic acid production, which can contribute to reduced virulence of S. sclerotiorum and lead to failure of disease infection. Protective and curative activity tests showed that pyrisoxazole exhibited excellent protective and curative activity against S. sclerotiorum in oilseed rape, and protective activity was better than curative activity. Compared with the currently used fungicides, pyrisoxazole not only exhibited excellent control efficacy on Sclerotinia stem rot, but also dramatically reduced the doses of fungicides in the field trials. Overall, these data provide more references for revealing pharmacological effect of pyrisoxazole against S. sclerotiorum and managing Sclerotinia stem rot on oilseed rape caused by benzimidazole- and dicarboximide-resistant populations.

Interference screw insertion angle has no effect on graft fixation strength for insertional Achilles tendon reconstruction.

PURPOSE: To compare the effect of two interference screw insertion angles on the biomechanical properties of the insertional Achilles tendon (IAT) reconstruction. METHODS: Nine matched pairs of fresh-frozen human cadaveric Achilles tendon specimens were randomized to two groups with interference screw insertion angles of 60° and 120°. The IAT reconstruction was performed by fixing the graft tendon with the interference screw. Each specimen was loaded to failure. The load at failure, stiffness, and mode of failure were documented. Differences in load at failure and stiffness were analysed. RESULTS: There was no statistically significant difference between the 60° and 120° groups for failure load (149.137 ± 20.836 versus 155.428 ± 28.343 N, respectively, n.s.) and stiffness (14.523 ± 2.824 N/mm versus 14.727 ± 2.192 N/mm, respectively, n.s.). The most common mode of failure was the graft pulling out of the bone tunnel when the screw broke. CONCLUSIONS: Graft fixation at two different interference screw insertion angles for IAT reconstruction exhibited equivalent biomechanical performance. When performing this procedure, surgeons may choose the interference screw insertion angle based on personal preference.

Treatment of talus osteochondral defects in chronic lateral unstable ankles: small-sized lateral chondral lesions had good clinical outcomes.

PURPOSE: To assess and compare the clinical and MRI outcomes of patients with talus osteochondral defect (OCD) and patients without OCD in a cohort with chronic lateral ankle instability. METHODS: All patients who underwent open or arthroscopic anterior talofibular ligament repair of the lateral ligament complex by a single surgeon were included in this study. Ankle arthroscopic surgery was initially performed to manage any intra-articular OCD, including debridement and microfracture. Functional scores (AOFAS, Karlsson score) and Tegner activity level scores were determined. An MRI scan was performed at follow-up to assess talus OCD after treatment. Spearman's correlation coefficients were calculated between functional scores and various factors. RESULTS: A total of 104 patients with chronic ankle instability were included in this study. Among them, 33 patients had cartilage injury on the talus (OCD group), and the other 71 patients had no cartilage injury (control group). After surgery, there was a significant increase in the AOFAS scores (p < 0.001), the Karlsson scores (p < 0.001), and the Tegner activity scores (p < 0.001) in both the OCD group and the control group. However, there was no significant difference in the AOFAS scores (90.7 ± 6.6 vs. 92.5 ± 8.5; n.s.), the Karlsson scores (89.7 ± 9.3 vs. 91.2 ± 9.1; n.s.), or the Tegner activity scores (5 vs. 6; n.s.) between the OCD group and the control group postoperatively. In the OCD group, there was a significant negative association between the functional scores (AOFAS, Karlsson score, or Tegner score) and the number of intra-articular lesions. For the lateral OCD, the mean lesion area significantly decreased from 49.0 ± 10.7 mm2 preoperatively to 18.3 ± 13.1 mm2 at the final follow-up (p < 0.001). CONCLUSION: No significant difference in functional outcomes was found between the OCD group and the control group postoperatively. Arthroscopic microfracture is a good option for the long-term treatment of lateral talus OCD. LEVEL OF EVIDENCE: III.

Arthroscopic treatment combined with the ankle stabilization procedure is effective for sinus tarsi syndrome in patients with chronic ankle instability.

PURPOSE: This study aimed to investigate the results of arthroscopic treatment combined with ankle stabilization procedure for sinus tarsi syndrome (STS) in patients with chronic ankle instability (CAI). METHODS: A total of 57 patients (31 males and 26 females, average age 29.9 ± 8.4 years ranging from 15 to 52 years) with STS and CAI who accepted operation from 2013 to 2015 were included in this retrospective study. Surgical procedures included thorough tarsal sinus debridement and repair or reconstruction of lateral ankle ligaments according to the quality of ligaments. American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson score, and Tegner score were evaluated preoperatively and at final follow-up. RESULTS: All the patients accepted thorough debridement of tarsal sinus. Of these, 53 patients (93.0%) had an arch structure between the posterior subtalar joint and the middle subtalar joint. Further, 54 patients accepted lateral ankle ligament repair, and 3 patients accepted ligament reconstruction. A total of 40 patients were followed up with an average time of 30.7 months. The modified AOFAS score increased from 62.5 (27-90) to 93 (67-100), the Karlsson score increased from 57 (30-82) to 90 (55-100), and the Tegner score increased from 1 (1-3) to 5 (1-8). CONCLUSIONS: Arthroscopic treatment combined with the ankle stabilization procedure could get satisfactory results for STS in patients with CAI. The arch structure composed by medial calcaneal component of the medial root of the inferior extensor retinaculum (MCC) might contribute to the pathological mechanism of STS. LEVEL OF EVIDENCE: IV.

Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives.

A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on (1)H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani, Sclerotinia sclerotiorum, Fusarium graminearum and Phytophthora capsici, by the mycelium growth inhibition method in vitro. Compound 5p exhibited significant anti-phytopathogenic activity, with the EC50 values of 0.18, 2.28, 1.01, and 1.85 µg mL(-1), respectively. In vivo testing demonstrated that 5p was effective in the control of rice sheath blight, rape sclerotinia rot and fusarium head blight. A 3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.

Modular Synthesis and Antimicrobial Investigation of Mycoleptodiscin A and Simplified Indolosesquiterpenoids.

The structure-activity relationship of the unusual indolosesquiterpenoid mycoleptodiscin A is unknown due to natural scarcity and inefficient synthesis. A modular approach leveraging Larock indole synthesis has been established to access mycoleptodiscin A and a divergent collection of drimenyl indoles. It features the utilization of an inexpensive (+)-sclareolide, modularity, purification-economy, and scalability, which facilitates the first biological evaluation of mycoleptodiscin A and related precursors.

Eudistomins Y-Inspired Design and Divergent Optimization of Heteroaryl Ketones for New Antifungal Leads.

The discovery of structurally distinct leads is imperative in modern agrochemical science. Inspired by eudistomins Y and the framework-related pharmaceuticals, aryl heteroaryl ketone was drawn as a common model intriguing the design and divergent synthesis of 14 kinds of heteroaryl ketones aligned with their oxime derivatives. Antifungal function-oriented phenotypical screen protruded benzothiazolyl-phenyl oxime 5a as a promising model, and the concomitant modification led to benzothiazolyl oxime 5am (EC50 = 5.17 µM) as a superior lead than fluoxastrobin (EC50 = 7.54 µM) against Sclerotinia sclerotiorum. Scaffold hopping of the phenyl subunit identified benzothiazolyl-pyridyl oxime as a novel antifungal scaffold accompanied by acquiring oxime 5bm with remarkable activity (EC50 = 3.57 µM) against Pyricularia oryzae. Molecular docking showed that candidate 5am could form more hydrogen bonds with the amino acid residues of actin than metrafenone. This compound also demonstrated better curative efficacy than that of fluoxastrobin and metrafenone in controlling the plant disease caused by S. sclerotiorum. These results rationalize the discovery of antifungal candidates based on aryl heteroaryl ketone.

Degradation-Risk-Inspired Optimization of the Antifungal Oxazolinyl Aniline Lead by a Fusion of Triazole with Nicotinamide.

The discovery of readily available and easily modifiable new models is a crucial and practical solution for agrochemical innovation. Antifungal function-oriented fusion of triazole with the prevalidated lead (R)-LE001 affords a novel framework with a broad and enhanced antifungal spectrum. Characterized by the easy accessibility and adjustability of [1,2,4]triazolo[4,3-a]pyridine, modular fine-tuning provided a set of unprecedented leads (e.g., Z23, Z25, Z26, etc.) with superior antifungal potentials than the positive control boscalid. Candidate Z23 exhibited a more promising antifungal activity against Sclerotinia sclerotiorum, Botrytis cinerea, and Phytophthora capsici with EC50 values of 0.7, 0.6, and 0.5 µM, respectively. This candidate could effectively control boscalid-resistant B. cinerea strains and also exhibit good vivo efficacy in controlling gray mold. Noteworthily, both the SDH-inhibition and the efficiency against Oomycete P. capsici are quite distinct from that of the positive control boscalid. A molecular docking simulation also differentiates Z23 from boscalid. These findings highlight the potential of [1,2,4]triazolo[4,3-a]pyridine amide as a novel antifungal model.

Multidimensional Optimization of R-LE001 for New Leads with Enhanced Antifungal Profiles.

Scaffold hopping and structural fine-tuning are important strategies for agrochemical innovation. Multidimensional optimization of the prevalidated antifungal lead R-LE001 was conducted via the design, synthesis, and bioevaluation of 53 new compounds differing in either scaffold or substituent. The antifungal structure-activity relationship (SAR) revealed that a number of amides containing 2-(2-oxazolinyl) aniline (NHPhOx) or 2-(2-thiazolinyl) aniline (NHPhthiOx) demonstrated a more promising antifungal effect than both R-LE001 and the positive control boscalid. Specifically, compound 10 (encoded LEX-K01) shows an excellent antifungal effect against Botrytis cinerea with an EC50 value lower than 0.11 µM. This small change leads to a significant improvement (over 1 order of magnitude) in bioactivity compared to that of either R-LE001 (EC50 = 1.41 µM) or boscalid (EC50 = 2.01 µM) and fluxapyroxad (EC50 = 4.35 µM). With much lower resistance factors, LEX-K01 (10) was more efficacious against the two boscalid-resistant strains of B. cinerea TZ01 and NJBH2017. A combination of LEX-K01 (10) and boscalid in a ratio of 1:3 showed synergistic effects against resistant B. cinerea TZ01 and NJBH2017, with SR values of 3.01 and 2.55, respectively. LEX-K01 (10) has a curative efficacy (70.3%) more prominent than that of boscalid (51.2%) in controlling disease caused by B. cinerea. The molecular docking simulation of LEX-K01 (10) with the SDH protein of B. cinerea displayed four hydrogen bonds with amino acid residues TYR144, ARG88, TRP81, and SER84, rationalizing a stronger affinity than boscalid. The scanning electron microscopy (SEM) characteristic revealed that it could cause an obvious collapse of B. cinerea mycelium. This work indicates that LEX-K01 (10) has the potential to be further explored as a new antifungal agent.

Design and Discovery of α-Oximido-arylacetamides as Novel Antifungal Leads.

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the o-aminophenyloxazoline (NHPhOx) scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead R-LE008. Fine-tuning of the α-position and scaffold hopping of acid segment and NHPhOx enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads CN19, CN21b, CN28, and CN31 against Sclerotinia sclerotiorum and Botrytis cinerea. The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable CN21 isomers. The Z-isomer (CN21b), with an EC50 value of 0.97 µM against B. cinerea, is significantly more potent than its E-isomer (CN21a) and the positive control boscalid. More importantly, compound CN21b can efficiently inhibit resistant B. cinerea strains. CN21b demonstrates a better in vivo preventative effect (82.1%) than those of CN21a (48.1%) and boscalid (55.1%) at 100 µM. CN21b showed a distinct binding model from those of the boscalid and CN21a in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of B. cinerea treated by CN21 isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing NHPhOx as a new model for agrochemical innovation.

Research on Optical Fiber Ring Resonator Q Value and Coupling Efficiency Optimization.

The coupling efficiency of the fiber ring resonator has an important influence on the scale factor of the resonant fiber gyroscope. In order to improve the scale factor of the gyroscope, the coupling efficiency of the fiber ring resonator and its influential factors on the scale factor of the gyroscope are analyzed and tested. The results show that the coupling efficiency is affected by both the splitting ratio of the coupler and the loss in the cavity. When the coupling efficiency approaches 0.75 at the under-coupling state, the scaling factor of the gyroscope is the highest. This provides a theoretical reference and an experimental basis for the enhancement of the scaling factor of the resonant fiber gyroscope with the fiber ring resonator as the sensitive unit, providing options for multiple applications such as sea, land, sky and space.

Antifungal Function Oriented Scaffold Hopping for the Discovery of Oxazolyl-oxazoline as a Novel Model against Fusarium graminearum.

Discovery of novel structural models is extremely important in agrochemical innovation. Scaffold hopping was conducted, and 16 kinds of novel models were synthesized and biologically evaluated. Oxazolyl-oxazoline 25 showed a promising in vitro potential against Fusarium graminearum with EC50 value of 18.25 µM, which was 2.4 times more potent than that of carbendazim (EC50 = 43.06 µM). The antifungal structure-activity relationship (SAR) revealed that compound 25am had the most promising antifungal activity against F. graminearum, with an EC50 value of 13.46 µM, which was 3.2 more potent than that of carbendazim. Different from carbendazim, the candidate 25am could form five hydrogen bonds with the amino acid residues in ß-tubulin in the molecular docking and could effectively inhibit the carbendazim-resistant F. graminearum strain. Scanning electron microscopy (SEM) revealed that compound 25am induced the mycelia of F. graminearum slight collapse. This work suggests that compound 25am should be prioritized for further evaluation for new antifungal agents.

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation. A panel of antifungal leads (LW2, LW3, and LW11) was acquired, showing much better antifungal performance than the positive controls. Specifically, compound LW3 exhibited a broad antifungal spectrum holding EC50 values as low as 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively. It demonstrated a curative efficacy better than that of boscalid in controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite different from that of the positive controls boscalid and fluopyram. This progress highlights the practicality of isoquinoline hydrazide as a novel model in fungicide innovation.

Chromatography-Free Synthesis of ß-Carboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of ß-Carbolines as Promising Antifungal and Antibacterial Candidates.

Agrochemical science prioritizes the discovery and effective synthesis of innovative and promising lead compounds. Herein, we developed an efficient column chromatography-free synthesis for ß-carboline 1-hydrazides via a mild CuBr2-catalyzed oxidation and investigated the antifungal and antibacterial activities and mechanisms for these compounds. In our study, compounds 4de (EC50 = 0.23 µg·mL-1) and 4dq (EC50 = 0.11 µg·mL-1) displayed the best efficacy, demonstrating enhancements in inhibitory activity of more than 20-fold against Ggt compared to silthiopham (EC50 = 2.39 µg·mL-1). Additionally, compound 4de (EC50 = 0.21 µg·mL-1) demonstrated outstanding in vitro antifungal activities as well as in vivo curative activities against Fg. According to preliminary mechanistic studies, ß-carboline 1-hydrazides led to the accumulation of reactive oxygen species, destruction of cell membranes, and dysregulation of histone acetylation. Furthermore, several substances exhibited antibacterial activity against Psg and Cms by preventing the development of bacterial biofilms.