Potential Fungicides Research Articles

In vitro/vivo antifungal activity study of novel mandelic acid derivatives as potential fungicides against Thanatephorus cucumeris

To discover highly efficient and novel lead compounds against Thanatephorus cucumeris, a series of novel mandelic acid derivatives containing 1,3,4-thiadiazole thioether was designed and synthesized. The bioassay results revealed that target compound F10 exhibited excellent antifungal activity against T. cucumeris with EC50 value of 9.7 μg/mL. Further studies found that F10 not only significantly inhibited the growth of T. cucumeris mycelia but also effectively inhibited the formation of sclerotia, and exhibited significant in vivo protective (61.1%) and curative (67.9%) activities at 200 μg/mL. Mechanism studies demonstrated that F10 can damage the integrity of the cell membrane structure, resulting in increased permeability of the cell membrane, releasing the intracellular electrolyte and inhibiting the growth of fungi. In general, this work is helpful for managing the formation and diffusion of the infection source and provides an effective method to control rice sheath blight disease infected with sclerotia of T. cucumeris.

Fungicidal effects of Commiphora swynnertonii (Burrt.) and Synadenium glaucescens (Pax.) against tomato fusarium wilt disease

Tomato fusarium wilt disease is an important soil-borne disease caused by Fusarium oxysporum f. sp. Lycopersici (FoL) worldwide. The disease causes yield losses of about 90% worldwide. This study aimed to evaluate the extracts of C. swynnertonii (resins) and S. glaucescens (latex, fresh and dry leaves) for their efficacy against FoL. In the laboratory, a 4 × 4 factorial experiment in a Complete Randomized Design (CRD) was carried out to evaluate resins, latex, fresh, and dry leaves each in four concentrations (0.01 g/ml, 0.05 g/ml, 0.1 g/ml and 0.15 g/ml). The negative and positive controls were Sterile Distilled Water (SDW) and a Linkmil 72 WP (Mancozeb 64% + Metalaxyl 8%) respectively. In a screenhouse, resins, latex, and fresh and dry leaves, each at 0.15 g/ml were applied on pre-inoculated tomato plants to manage TFW disease. The experiment was laid out in a Randomized Complete Block Design (RCBD) with four replications. The negative and positive controls were the untreated soil and soil treated with Linkmil 72 WP respectively. The differences between extracts in the inhibition of radial mycelial growth of the pathogen were highly significant (p = 0.000). The efficacy of the plant extracts against in vitro growth of FoL was significantly dependent on the application dose. The inhibition of mycelial growth caused by latex and dry leaves was higher than that of Linkmil 72 WP (23.58%) and SDW (0%) by 41% and 65% respectively. Findings show that there was a TFW disease reduction of 72.92% 68.75% and 56.25% in plants treated with dry leaves, the latex of S. glaucescens, and resin of C. swynnertonii in that order. Plant extracts had significant effects (p = 0.000) on plant growth. The plants treated with dried leaf powder attained the highest height, the number of branches/plant, leaves/plant, and leaf area of 85.85 cm, 19.25,99.5 and 59.39 respectively. The findings benchmark the fungicidal potential of C. swynnertonii and S. glaucescens.

In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaportheoryzae

Magnaporthe oryzae causes destructive blast disease in more than 50 species of the major cereal crops rice, wheat and maize and destroys food of millions of people worldwide. Application of synthetic chemical fungicides are environmentally hazardous and unreliable in controlling M. oryzae. Conversely, naturally occurring biofungicides with multiple modes of actions are needed to be discovered for combatting the blast fungus. To find the effective biofungicides, we performed molecular docking study of some potential antifungal natural compounds targeting two proteins including a single-stranded DNA binding protein MoSub1 (4AGH), and an effector protein AVR-Pik (5E9G) of M. oryzae that regulates transcription in fungus and/or suppresses the host cell immunity. The thirty-nine natural compounds previously shown to inhibit M. oryzae growth and reproduction were put under molecular docking against these two proteins followed by simulation, free energy, and interaction analysis of protein-ligand complexes. The virtual screening revealed that two alkaloidal metabolites, camptothecin and GKK1032A2 showed excellent binding energy with any of these target proteins compared to reference commercial fungicides, azoxystrobin and strobilurin. Of the detected compounds, GKK1032A2 bound to both target proteins of M. oryzae. Both compounds showed excellent bioactivity scores as compared to the reference fungicides. Results of our computational biological study suggest that both camptothecin and GKK1032A2 are potential fungicides that could also be considered as lead compounds to design novel fungicides against the blast fungus. Furthermore, the GKK1032A2 acted as a multi-site mode of action fungicide against M. oryzae.

Harnessing fungicide potential of hydrothermal liquefaction water from livestock manure: A new vision of integrated crop-livestock system

Hydrothermal liquefaction (HTL) can turn livestock manure into biocrude oil, but the aqueous phase (HTL-AP) attracts increasing concerns owing to its large amount and high toxicity. In this regard, a novel integrated crop-livestock system paradigm was proposed where HTL-AP from livestock manure was used as fungicide for phytopathogen control. To verify this strategy, Alternaria solani was employed as indicator phytopathogen, whereas cow manure (CM) and swine manure (SM) were used as the feedstock to obtain fungicide compounds via hydrothermal liquefaction (HTL). Results showed that the minimum inhibition concentration (MIC) of two HTL-APs was about 12%, where the main active compounds probably were phenols and nitrogenous compounds. The fungicide application would increase the manure carrying capacity by over 10%. Further observation revealed that HTL-AP exhibited inhibition through multiple pathways such as changing the mycelial morphology and cell membrane structure, resulting in metabolic disorders via impacting the generation of H2O2, ATP, reducing sugar and protein. The synergistic interaction among pathways was finally analyzed. Then, the effect of HTL-AP on seed-borne fungi control was evaluated via 36 groups of seed germination tests. For all that, this study provides new insights into the valorization of HTL-AP form livestock manure via unlocking its potential as sustainable fungicide constituents for phytopathogen control, further contributes to green development of current integrated crop-livestock system.

PCR–RFLP analysis for detecting potential QoI and CAA fungicide resistance in onion and lettuce downy mildews

PCR–RFLP analysis for detecting potential QoI and CAA fungicide resistance in onion and lettuce downy mildews

Evaluation of In Vitro and In Vivo Antifungal Activity of Green Synthesized Silver Nanoparticles against Early Blight in Tomato

Silver nanoparticles have gained considerable interest in recent decades due to their antimicrobial activity and are used in water disinfection, wound healing, food packaging, and plant protection. This study tested the potential of silver nanoparticles synthesized using the neem (Azadirachta indica) leaf extract against Alternaria solani causes early blight disease in tomato plants. The pathogen was isolated from infected tomato plants and identified using morphological and molecular features. The results showed significant variation among isolates. Isolates, Shk-1 and Ksr-1 were highly pathogenic, causing up to 80% disease incidence. The potential of silver nanoparticles against each isolate was determined using different concentrations of silver nanoparticles. During in vitro and in vivo experiments, the growth inhibition rate of the pathogen was 70–100% at 50 ppm. Lower concentrations of silver nanoparticles (5 and 10 ppm) increased phenolics, PO, PPO, and PAL production by more than 50% as compared to the untreated control. These defensive mechanisms clearly demonstrate the fungicidal potential of AgNPs and recommend their utilization in different crop protection programs.

FUNGITOXITY OF Mentha spicata OIL ON THE GROWTH OF FUNGI OF THE GENERA Colletotrichum AND Fusarium

Increasingly, the population has been concerned that the production of these foods is free of pesticide residues, so it is necessary to search for viable and effective alternatives to control pests and diseases. Thus, the use of essential oil from plants with insecticidal and fungicidal potential has been successfully studied. The study aimed to demonstrate the effect of Mentha spicata essential oil on the control of Fusarium and Colletotrichum fungi in vitro. The essential oil of M. spicata used was purchased from the chemical industry Ferquima, being diluted in a 2% Tween 20 solution (being 98 mL of distilled water + 2 mL of Tween 20), which was added in 60 mL of a PDA culture medium, resulting in final essential oil concentrations: 0 ppm; 0.83 ppm; 1.67 ppm; 8.33 ppm, and 16.67 ppm and poured into 90 mm diameter Petri dishes. The evaluations took place periodically every 48 hours for eight days, performing measurements of the diameters of the colonies. The results evidenced that the analyzed fungi, when submitted to treatments of different doses, suffered fungistatic action according to the gradual increase of the doses. Thus, it is possible to conclude that M. spicata oil provided the in vitro growth control of Fusarium sp. and Colletorichum sp.

Management of mung bean leaf spot disease caused by Phoma herbarum through Penicillium janczewskii metabolites mediated by MAPK signaling cascade

Vigna radiata L., an imperative legume crop of Pakistan, faces hordes of damage due to fungi; infecting host tissues by the appressorium. The use of natural compounds is an innovative concern to manage mung-bean fungal diseases. The bioactive secondary metabolites of Penicillium species are well documented for their strong fungi-static ability against many pathogens. Presently, one-month-old aqueous culture filtrates of Penicillium janczewskii, P. digitatum, P. verrucosum, P. crustosum, and P. oxalicum were evaluated to check the antagonistic effect of different dilutions (0, 10, 20, … and 60%). There was a significant reduction of around 7–38%, 46–57%, 46–58%, 27–68%, and 21–51% in Phoma herbarum dry biomass production due to P. janczewskii, P. digitatum, P. verrucosum, P. crustosum, and P. oxalicum, respectively. Inhibition constants determined by a regression equation demonstrated the most significant inhibition by P. janczewskii. Finally, using real-time reverse transcription PCR (qPCR) the effect of P. Janczewskii metabolites was determined on the transcript level of StSTE12 gene involved in the development and penetration of appressorium. The expression pattern of the StSTE12 gene was determined by percent Knockdown (%KD) expression that was found to be decreased i.e. 51.47, 43.22, 40.67, 38.01, 35.97, and 33.41% for P. herbarum with an increase in metabolites concentrations viz., 10, 20, 30, 40, 50 and 60% metabolites, respectively. In silico studies were conducted to analyze the role of Ste12 a transcriptional factor in the MAPK signaling pathway. The present study concludes a strong fungicidal potential of Penicillium species against P. herbarum. Further studies to isolate the effective fungicidal constituents of Penicillium species through GCMS analysis and determination of their role in signaling pathways are requisite.

Exploring the nano-fungicidal efficacy of green synthesized magnesium oxide nanoparticles (MgO NPs) on the development, physiology, and infection of carrot (Daucus carota L.) with Alternaria leaf blight (ALB): Molecular docking

In this research, green synthesized magnesium oxide nanoparticles (MgO NPs) from lemon fruit extracts and their fungicidal potential was evaluated against Alternaria dauci infection on carrot (Daucus carota L.) under greenhouse conditions. The scanning and transmission electron microscopy (SEM and TEM) and ultra-violet (UV) visible spectroscopy were used to validate and characterize MgO NPs. The crystalline nature of MgONPs was determined using selected area electron diffraction (SAED). MgO NPs triggered substantial antifungal activity against A. dauci when exposed to 50 and 100 mg L−1 concentrations but the higher antifungal potential was noticed in 100 mg L−1 under in-vitro conditions. In fungal inoculated plants, a marked decrease in growth, photosynthetic pigments, and an increase in phenol, proline contents, and defense-related enzymes of carrot were seen over control (distilled water). However, foliar application of MgO NPs at 50 and 100 mg L−1 resulted in significant improvement of plant growth, photosynthetic pigments, phenol and proline contents, and defense enzymes activity of carrots with and without A. dauci infection. Spraying of MgO NPs at 100 mg L−1 had more plant length (17.11%), shoot dry weight (34.38%), plant fresh weight (20.46%), and root dry weight (49.09%) in carrots when challenged with A. dauci over inoculated control. The leaf blight indices and percent disease severity were also reduced in A. dauci inoculated plants when sprayed with MgO NPs. The non-bonding interactions of Alternaria genus protein with nanoparticles were studied using molecular docking.

Discovery of HNPC-A9229: A Novel Pyridin-2-yloxy-Based Pyrimidin-4-amine Fungicide.

To search for novel pesticides, the synthesis around commercialized insecticide tebufenpyrad accidentally led us to the discovery of the fungicidal lead compound, 3-ethyl-1-methyl-N-((2-phenylthiazol-4-yl)methyl)-1H-pyrazole-5-carboxamide (1a) and its pyrimidin-4-amine-based optimization derivative 5-chloro-2,6-dimethyl-N-(1-(2-(p-tolyl)thiazol-4-yl)ethyl)pyrimidin-4-amine (2a). Compound 2a not only demonstrates fungicidal activity superior to commercial fungicides such as diflumetorim but also exhibits the good features that come with pyrimidin-4-amines, such as unique modes of action and no cross-resistance to other pesticide classes. However, 2a is highly toxic to rats. Further optimization of 2a by introducing pyridin-2-yloxy substructure finally led to the discovery of 5b5-6 (HNPC-A9229) (5-chloro-N-(1-((3-chloropyridin-2-yl)oxy)propan-2-yl)-6-(difluoromethyl)pyrimidin-4-amine). HNPC-A9229 exhibits excellent fungicidal activities with EC50 values of 0.16 mg/L against Puccinia sorghi and 1.14 mg/L against Erysiphe graminis, respectively. Not only that its fungicidal potency is significantly superior to or comparable to commercial fungicides including diflumetorim, tebuconazole, flusilazole, and isopyrazam, HNPC-A9229 possesses low toxicity to rats.

Sequence analysis of cytochrome b gene in Vietnamese isolates of Hemileia vastatrix, the causal agent of coffee leaf rust, in relation to potential QoI fungicide resistance

Sequence analysis of cytochrome b gene in Vietnamese isolates of Hemileia vastatrix, the causal agent of coffee leaf rust, in relation to potential QoI fungicide resistance

Discovery of Terpene-Derived Quaternary Ring Compounds Containing an Oxime Moiety as Potential Fungicides.

Terpene-derived quaternary ring compounds with an oxime moiety were designed and prepared to create fungicides from natural products. A preliminary assessment of their antifungal activity against seven common pathogenic fungi was conducted, and the median effective concentration (EC50) values against Rhizoctonia solani were obtained. The effects of compound 6a19 (3-bromothiophene-containing), which had an outstanding EC50 value (1.62 μg/mL), on the morphology, ultrastructure, reactive oxygen species production, mitochondrial membrane potential, nuclear morphology, and defense-related and respiration-related enzyme activities of mycelia were evaluated. The test compound was speculated to obstruct the bio-oxidative process, inhibiting mycelial growth. Compound 6a19 exhibited a satisfactory in vivo control effect on leaf sheath-infected rice plants. After treating rice plants with 50, 100, and 200 μg/mL 6a19, the protective and therapeutic efficacy values were 48.3 and 70.3%, 58.6 and 75.7%, and 69.0 and 81.1%, respectively. Moreover, a linear quantitative structure-activity relationship (R2 = 0.932, F = 61.3, and S2 = 0.020) was established using density functional theory calculations. Four chemical descriptors that were crucial to the antifungal activity were analyzed: the number of occupied electronic levels of atoms, the minimum atomic orbital electronic population, maximum net atom charge for a H atom, and minimum net atomic charge. In overall consideration of experimental results, it was speculated that the target compounds satisfactorily inhibited R. solani by interfering with biological oxidation pathways, which provided an insight into the future intensive and systematic action mechanism. This research is promising for the invention of novel fungicides from natural terpenes with multiple potential targets and satisfactory ecological compatibility.

Synthesis, anti-oomycete and fungal activities of resveratrol sulfonate derivatives containing three esters moieties

In order to explore novel natural product-based anti-oomycete and fungal agents, thirteen unreported resveratrol sulfonate derivatives containing three esters moieties were designed and prepared using the principle of activity superposition, and structurally confirmed by 1H NMR, 13C NMR, HRMS, and m.p. Furthermore, we evaluated the target compounds (3a–m) as anti-oomycete and fungal activities against two serious agricultural diseases of Phytophthora capsici and Fusarium graminearum, respectively. Among the thirteen resveratrol sulfonate derivatives tested, three compounds 3d, 3k, and 3l exhibited the most potent anti-oomycete activity against P. capsici with EC50 values of 27.31, 27.69, and 26.14 mg/L, respectively. Moreover, two compounds 3e and 3l exhibited the most potent anti-fungal activity against F. graminearum with EC50 values of 75.81, and 73.60 mg/L, respectively. Overall, the anti-oomycete activity against P. capsici of the target compound was significantly better than that of the anti-fungal activity against F. graminearum. In particular, anti-oomycete and fungal activities showed that the structural skeleton presentation activity was closely related to the different substituents of the sulfonyloxy groups, especially the anti-oomycete activity. This study will lay a solid foundation for further modifying resveratrol to develop potential new fungicides.

Design and synthesis of novel benzoxazole/chromene-phthalide scaffolds hybrids as potential natural products-based fungicide

Phthalide, benzoxazole, and chromene are important heterocyclic skeletons with extensive biological activities. In order to develop novel potential antifungal agents, twenty-two benzoxazole/chromene-containing phthalide derivatives were prepared, and their fungicidal activity against nine common plants pathogenic fungi were evaluated in vitro. The EC50 values indicated that compound Z-4b displayed superior antifungal activity against P. oryzae (11.0 μg/mL), F. solani (8.5 μg/mL), P. capsici (27.8 μg/mL), V. mali (3.1 μg/mL) and A. brassicae (4.3 μg/mL) strains, which was more potent than the two commercialized fungicides hymexazol and chlorothalonil. In addition, the structure-activity relationship analysis demonstrated that the combination site of oxazolamide with phthalide has an important effect on antifungal activity. This research offers a potential compound for the development of novel agricultural fungicides.

Intravaginal delivery for CRISPR-Cas9 technology: For example, the treatment of HPV infection.

The increasing incidence of sexually transmitted diseasesin women, including human papillomavirus (HPV) infection, has led to the need to develop user-friendly potential prevention methods. At present, although there are several therapeutic parts, none of them has a preventive effect, but they are only limited to providing patients with symptom relief. Researchers have now recognized the need to find effective local preventive agents. One of the potential undiscovered local fungicides is the vaginal delivery of CRISPR/Cas9. CRISPR/Cas9 delivery involves silencing gene expression in a sequence-specific manner in the pathogenic agent, thus showing microbicidal activity. However, vaginal mucosal barrier and physiological changes (such as pH value and variable epithelial thickness in the menstrual cycle) are the main obstacles to effective delivery and cell uptake of CRISPR/Cas9. To enhance the vaginal delivery of CRISPR/Cas9, so far, nano-carrier systems such as lipid delivery systems, macromolecular systems, polymer nanoparticles, aptamers, and cell-penetrating peptides have been extensively studied. In this paper, various nano-carriers and their prospects in the preclinical stage are described, as well as the future significance of CRISPR/Cas9 vaginal delivery based on nano-carriers.

Potential Fungicide Candidates: A Dual Action Mode Study of Novel Pyrazole-4-carboxamides against Gibberella zeae

Pyrazole carboxamides are a class of traditional succinate dehydrogenase inhibitors (SDHIs) that have developed into a variety of commercialized fungicides. In the present work, a series of novel 1,5-disubstituted-1H-pyrazole-4-carboxamide derivatives were designed and synthesized based on the active backbone of 5-trifluoromethyl-1H-4-pyrazole carboxamide. Bioassay results indicated that some target compounds exhibited excellent in vitro antifungal activities against six phytopathogenic fungi. Notably, the EC50 values of Y47 against Gibberella zeae, Nigrospora oryzae, Thanatephorus cucumeris, and Verticillium dahliae were 5.2, 9.2, 12.8, and 17.6 mg/L, respectively. The in vivo protective and curative activities of Y47 at 100 mg/L against G. zeae on maize were 50.7 and 44.2%, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis revealed that the large steric hindrance and electronegative groups on the 5-position of the pyrazole ring were important for the activity. The IC50 value of Y47 against succinate dehydrogenase (SDH) was 7.7 mg/L, superior to fluopyram (24.7 mg/L), which was consistent with the docking results. Morphological studies with fluorescence microscopy (FM) and scanning electron microscopy (SEM) found that Y47 could affect the membrane integrity of mycelium by inducing endogenous reactive oxygen species (ROS) production and causing peroxidation of cellular lipids, which was further verified by the malondialdehyde (MDA) content. Antifungal mechanism analysis demonstrated that the target compound Y47 not only had significant SDH inhibition activity but could also affect the membrane integrity of mycelium, exhibiting obvious dual action modes. This research provides a novel approach to the development of traditional SDHIs and their derivatives.

Novel quinolin-2(1H)-one analogues as potential fungicides targeting succinate dehydrogenase: design, synthesis, inhibitory evaluation and molecular modeling.

Succinate dehydrogenase is an important target of fungicides. Succinate dehydrogenase inhibitors (SDHIs) have widely been used to combat destructive plant pathogenic fungi because they possess efficient and broad-spectrum antifungal activities and as well as unique mode of action. The research and development of novel SDHIs have been ongoing. Thirty-six novel quinolin-2(1H)-one derivatives were designed, synthesized and characterized. The single crystal structure of compound 3c was determined through the X-ray diffraction of single crystals. The bioassay results displayed that most compounds had good antifungal activities at 16 μg mL-1 against Rhizoctonia cerealis, Erysiphe graminis, Botrytis cinerea, Penicillium italicum and Phytophthora infestans. Compounds 6o, 6p and 6r had better antifungal activities than the commercialized fungicide pyraziflumid against Botrytis cinerea. Their half maximal effective concentration (EC50 ) values were 0.398, 0.513, 0.205 and 0.706 μg mL-1 , respectively. Moreover, the inhibiting activities of the bioactive compounds were tested against succinate dehydrogenase. The results indicated that they possessed outstanding activities. Compounds 6o, 6p and 6r also exhibited better inhibiting activities than pyraziflumid against succinate dehydrogenase. Their half maximal inhibitory concentration (IC50 ) values were 0.450, 0.672, 0.232 and 0.858 μg mL-1 , respectively. The results of molecular dynamic (MD) simulations indicated that compound 6r displayed stronger affinity to succinate dehydrogenase than pyraziflumid. The results of the present study displayed that quinolin-2(1H)-one derivative could be one scaffold of potential SDHIs and will provide some valuable information for the research and development of new SDHIs. © 2022 Society of Chemical Industry.

EFEKTIVITAS HERBISIDA NABATI EKSTRAK DAUN KETAPANG (Terminalia catappa L.) TERHADAP GULMA Asystasia gangetica L.

Asystasia gangetica is considered one of the invasive weeds and is often found in residential areas and is one of the most important weeds to plant. The aim of the study was to evaluate the effectiveness of the interaction between extract concentration and leaf condition of Terminalia catappa L. extracted from Asystasia gangetica. The study was conducted using a completely randomized design using two factors. The first factor was the condition of the extracted leaves, which were fresh, newly fallen and dried leaves. The second factor was the extract concentrations, which were 50, 75 and 100%. The parameters were the time of germination, the height of the plant, the number of leaves, the length of the root and the weight of the grass. The results of the experiment showed that there was an interaction between the extract concentration and the state of the extracted Terminalia catappa Leaf with all the observed parameters. In general, growth retardation increased with increasing extract concentration. Fungicidal potency was shown by the extract obtained from fresh leaves, followed by the extract from newly fallen leaves and the least from dried leaves.

4-Disubstituted Pyrazolin-3-Ones—Novel Class of Fungicides against Phytopathogenic Fungi

The search for fungicides of novel classes is the long-standing priority in crop protection due to the continuous development of fungal resistance against currently used types of active compounds. Recently, 4-nitropyrazolin-3-ones were discovered as highly potent fungicides, of which activity was believed to be strongly associated with the presence of a nitro group in the pyrazolone ring. In this paper, a series of 4-substituted pyrazolin-3-ones were synthesized and their fungicidal activity against an important species of phytopathogenic fungi (Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, and Sclerotinia sclerotiorum) was tested in vitro. We discovered that 4-mono and 4,4-dihalogenated pyrazolin-3-ones demonstrate fungicidal activity comparable to that of 4-nitropyrazolin-3-ones and other modern fungicides (such as kresoxim methyl). This discovery indicates that NO2 moiety can be replaced by other groups of comparable size and electronic properties without the loss of fungicidal activity and significantly expands the scope of potent new fungicides based on a pyrazolin-3-one fragment.

Design, green synthesis, and quorum sensing quenching potential of novel 2-oxo-pyridines containing a thiophene/furan scaffold and targeting a LasR gene on P. aeruginosa.

The current trend in fighting bacteria is attacking the virulence and quorum-sensing (QS) signals that control bacterial communication and virulence factors, especially biofilm formation. This study reports new Schiff bases and tetracyclic rings based on a pyridine pharmacophore by two methods: a green approach using CAN and a conventional method. The structure of designed derivatives was confirmed using different spectroscopies (IR and 1H/13C NMR) and elemental analysis. The designed derivatives exhibited good to moderate inhibition zones against bacterial and fungal pathogens. In addition, six compounds 2a,b, 3a,b, and 6a,b displayed potency against tested pathogens with eligible MIC and MBC values compared to standard antimicrobial agents. Compound 2a displayed MIC values of 15.6 μg mL-1 compared to Gentamicin (MIC = 250 μg mL-1 against K. pneumoniae), while compound 6b exhibited super-potent activity against P. aeruginosa, and K. pneumoniae with MIC values of 62.5 and 125 μg mL-1, as well as MBC values of 31.25 and 15.6 μg mL-1 compared to Gentamicin (MIC = 250 and 125 μg mL-1 and MBC = 62.5 μg mL-1), respectively. Surprisingly, these six derivatives revealed bactericidal and fungicidal potency and remarkable anti-biofilm activity that could significantly reduce the biofilm formation against MRSA, E. coli, P. aeruginosa, and C. albicans. Furthermore, the most active derivatives reduced the LasR gene's production between 10-40% at 1/8 MICs compared with untreated P. aeruginosa. Besides, they demonstrated promising safety profile on Vero cells (normal cell lines) with IC50 values ranging between (175.17 ± 3.49 to 344.27 ± 3.81 μg mL-1). In addition, the in silico ADMET prediction was carried out and the results revealed that these compounds could be used with oral bioavailability with low toxicity prediction when administered as a candidate drug. Finally, the molecular docking simulation was performed inside LasR and predicted the key binding interactions responsible for the activity that corroborated the biological results.