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With the intention of advancing our research on diverse C-20 derivatives of camptothecin (CPT), 38 CPT derivatives bearing sulphonamide and sulfonylurea chemical scaffolds and different substituent groups have been designed, synthesised and evaluated in vitro for cytotoxicity against four tumour cell lines, A-549 (lung carcinoma), KB (nasopharyngeal carcinoma), MDA-MB-231 (triple-negative breast cancer) and KBvin (an MDR KB subiline). As a result, all the synthesised compounds showed promising in vitro cytotoxic activity against the four cancer cell lines tested, and were more potent than irinotecan. Importantly, compounds 12b, 12f, 12j and 13 l possessed better antiproliferative activity against all tested tumour cell lines with IC50 values of 0.0118 - 0.5478 µM, and resulted approximately 3 to 4 times more cytotoxic than topotecan against multidrug-resistant KBvin subline. Convincing evidences are achieved that incorporation of sulphonamide and sulfonylurea motifs into position-20 of camptothecin confers markedly enhanced cytotoxic activity against cancer cell lines.
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BACKGROUND: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria. RESULTS: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC50 value against Botrytis cinerea was 1.34 µg mL-1. Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC90 values of 3.12 µg mL-1 and 1.56 µg mL-1. A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight. CONCLUSION: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry.
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Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv oryzae (Xoo) is extremely harmful to rice production. The traditional control approach is to use bactericides that target key bacterial growth factors, but the selection pressure on the pathogen makes resistant strains the dominant bacterial strains, leading to a decline in bactericidal efficacy. Type III secretion system (T3SS) is a conserved and critical virulence factor in most Gram-negative bacteria, and its expression or absence does not affect bacterial growth, rendering it an ideal target for creating drugs against Gram-negative pathogens. In this work, we synthesized a range of derivatives from cryptolepine and neocryptolepine. We found that compound Z-8 could inhibit the expression of Xoo T3SS-related genes without affecting the growth of bacteria. an in vivo bioassay showed that compound Z-8 could effectively reduce the hypersensitive response (HR) induced by Xoo in tobacco and reduce the pathogenicity of Xoo in rice. Furthermore, it exhibited synergy in control of bacterial leaf blight when combined with the quorum quenching bacterial F20.
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Alcaloides , Alcaloides Indólicos , Oryza , Quinolinas , Xanthomonas , Oryza/genética , Sistemas de Secreción Tipo III/genética , Bacterias/metabolismo , Xanthomonas/genética , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiologíaRESUMEN
The emergence of resistant pathogens has increased the demand for alternative fungicides. The use of natural products as chemical scaffolds is a potential method for developing fungicides. HWY-289, a semisynthetic protoberberine derivative, demonstrated broad-spectrum and potent activities against phytopathogenic fungi, particularly Botrytis cinerea (with EC50 values of 1.34 µg/mL). SEM and TEM imaging indicated that HWY-289 altered the morphology of the mycelium and the internal structure of cells. Transcriptomics revealed that it could break down cellular walls through amino acid sugar and nucleotide sugar metabolism. In addition, it substantially decreased chitinase activity and chitin synthase gene (BcCHSV) expression by 53.03 and 82.18% at 1.5 µg/mL, respectively. Moreover, this impacted the permeability and integrity of cell membranes. Finally, HWY-289 also hindered energy metabolism, resulting in a significant reduction of ATP content, ATPase activities, and key enzyme activities in the TCA cycle. Therefore, HWY-289 may be a potential candidate for the development of plant fungicides.
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Antifúngicos , Alcaloides de Berberina , Berberina/análogos & derivados , Fungicidas Industriales , Antifúngicos/farmacología , Antifúngicos/química , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Botrytis , Azúcares , Enfermedades de las Plantas/microbiologíaRESUMEN
Based on the research strategy of "drug repurposing", a series of derivatives and marketed drugs that containing salicylic acid skeleton were tested for their antibacterial activities against phytopathogens. Salicylic acid can not only regulate some important growth metabolism of plants, but also induce plant disease resistance. The bioassay results showed that the salicylamides exhibited excellent antibacterial activity. Especially, oxyclozanide showed the best antibacterial effect against Xanthomonas oryzae, Xanthomonas axonopodis pv. citri and Pectobacterium atroseptica with MICs of 0.78, 3.12 and 12.5â µg.mL-1, respectively. In vivo experiments with rice bacterial leaf blight had further demonstrated that oxyclozanide exhibited stronger antibacterial activity than the commercial bactericide, thiodiazole copper. Oxyclozanide could induce plant defense responses through the determination of salicylic acid content and the activities of defense-related enzymes including CAT, POD, and SOD in rice. The preliminarily antibacterial mechanism study indicated that oxyclozanide exhibited the antibacterial activity by disrupting cell integrity and reducing bacterial pathogenicity. Additionally, oxyclozanide could induce plant defense responses through the determination of salicylic acid content.
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Oryza , Xanthomonas , Salicilamidas/farmacología , Reposicionamiento de Medicamentos , Oxiclozanida/farmacología , Antibacterianos/farmacología , Oryza/microbiología , Pruebas de Sensibilidad Microbiana , Ácido Salicílico/farmacología , Enfermedades de las Plantas/prevención & control , Enfermedades de las Plantas/microbiología , Oxadiazoles/farmacologíaRESUMEN
BACKGROUND: Chemical fungicides are the mainstay of plant disease control in agricultural production, but there are a very limited number of drugs that can effectively control plant diseases. Two series of secondary amine derivatives were synthesized using the diamine skeleton combined with saturated aromatic and aliphatic aldehydes, and their antibacterial and antifungal activities against plant pathogens were determined. In addition, the antimicrobial mechanism of the highly active compound A26 was preliminarily examined against Xanthomonas oryzae (Xoo). RESULTS: Compound A26 exhibited the highest antibacterial potency among all the target compounds, with MIC values of 3.12, 3.12 and 12.5 µg mL-1 against Xoo, Xanthomonas axonopodis pv. Citri and Pseudomonas sollamacearum, respectively. In addition, compound A26 had powerful curative and protective effects against Xoo at 200 µg mL-1 , and was better than the control agent Xinjunan. Preliminary mechanistic studies showed that compound A26 reduced the bacterial pathogenicity by targeting cell membranes and inhibiting the secretion of extracellular polysaccharides. Meanwhile, the toxicity of compound A26 to Human Embryonic Kidney 293 cells and Human Liver-7702 was similar to that of Xinjunan, and it had moderate toxicity according to the World Health Organization classification standard of oral exogenous toxicity, with an LD50 of 245.47 mg kg-1 . CONCLUSION: Secondary amines have efficient and broad-spectrum antibacterial activity against plant pathogenic bacteria and are expected to be a new class of candidate compounds for antibacterial drugs. © 2023 Society of Chemical Industry.
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Oryza , Xanthomonas , Humanos , Pruebas de Sensibilidad Microbiana , Oxadiazoles/química , Antibacterianos/farmacología , Antibacterianos/química , Poliaminas/farmacología , Enfermedades de las PlantasRESUMEN
Since the first natural carbazole alkaloid, murrayanine, was isolated from Mwraya Spreng, carbazole alkaloid derivatives have been widely concerned for their anti-tumor, anti-viral and anti-bacterial activities. In recent decades, a growing body of data suggest that carbazole alkaloids and their derivatives have different biological activities. This is the first comprehensive description of the antifungal and antibacterial activities of carbazole alkaloids in the past decade (2012-2022), including natural and partially synthesized carbazole alkaloids in the past decade. Finally, the challenges and problems faced by this kind of alkaloids are summarized. This paper will be helpful for further exploration of this kind of alkaloids.
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Alcaloides , Antineoplásicos , Alcaloides/farmacología , Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Carbazoles/farmacología , Estructura MolecularRESUMEN
Aspergillus flavus, a widespread saprotrophic filamentous fungus, could colonize agricultural crops with aflatoxin contamination, which endangers food security and the agricultural economy. A safe, effective and environmentally friendly fungicide is urgently needed. Pterostilbene, a natural phytoalexin originated from Pterocarpus indicus Willd., Vaccinium spp. and Vitis vinifera L., has been reported to possess excellent antimicrobial activity. More importantly, it is quite safe and healthy. In our screening tests of plant polyphenols for the inhibition of A. flavus, we found that pterostilbene evidently inhibited mycelial growth of Aspergillus flavus (EC50 = 15.94 µg/mL) and the inhibitory effect was better than that of natamycin (EC50 = 22.01 µg/mL), which is a natural product widely used in food preservation. Therefore, we provided insights into the efficacy of pterostilbene suppression on A. flavus growth, aflatoxin B1 biosynthesis and its potential mechanisms against A. flavus in the present study. Here, pterostilbene at concentrations of 250 and 500 µg/mL could effectively inhibit the infection of A. flavus on peanuts. And the biosynthesis of the secondary metabolite aflatoxin B1 was also inhibited. The antifungal effects of pterostilbene are exerted by inducing a large amount of intracellular reactive oxygen species production to bring the cells into a state of oxidative stress, damaging cellular biomolecules such as DNA, proteins and lipids and destroying the integrity of the cell membrane. Taken together, our study strongly supported the fact that pterostilbene could be considered a safe and effective antifungal agent against A. flavus infection.
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Aflatoxinas , Aspergillus flavus , Aspergillus flavus/metabolismo , Aflatoxina B1 , Antifúngicos/farmacología , Antifúngicos/metabolismoRESUMEN
Primary liver cancer is one of the most common malignant cancers of the digestive system that lacks effective chemotherapeutic drugs in clinical settings. Camptothecin (CPT) and its derivatives have been approved for cancer treatment; however, their application is limited by their systemic toxicity. For lead optimization in new drug discovery stages, fluorination is an effective and robust approach to increase the bioavailability and optimize the pharmacokinetics of candidate compounds, thereby improving their efficacy. To obtain new and highly active CPT derivatives, we designed, synthesized, and evaluated two new fluorinated CPT derivatives, 9-fluorocamptothecin (A1) and 7-ethyl-9-fluorocamptothecin (A2), in this study. In vitro, A1 and A2 exhibited more robust anti-tumor activity than topotecan (TPT) in various cancer cells, particularly hepatocellular carcinoma (HCC) cells. In vivo, A1 and A2 exhibited greater anti-tumor activity than TPT in both AKT/Met induced primary HCC mouse models and implanted HepG2 cell xenografts. Acute toxicity tests revealed that A1 and A2 were not lethal and did not cause significant body weight loss at high doses. Moreover, A1 and A2 exhibited no significant toxicity in the mouse liver, heart, lung, spleen, kidney, and hematopoietic systems at therapeutic doses. Mechanistically, A1 and A2 blocked HCC cell proliferation by inhibiting the enzymatic activity of Topo I, subsequently inducing DNA damage, cell cycle arrest, and apoptosis. In summary, our results indicate that fluorination improves the anti-tumor activity of CPT while decreasing its toxicity and highlight the application potential of fluorination products A1 and A2 in clinical settings.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Camptotecina/farmacología , Camptotecina/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , ADN-Topoisomerasas de Tipo I/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Topotecan/farmacología , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: The unreasonable use of chemical fungicides causes common adverse consequences that not only affect the environment, but also cause resistance and resurgence problems of plant pathogens, which are extremely harmful to human health, the economy, and the environment. Based on the rich biological activities of boron-based compounds, 82 phenylboronic acid derivatives were selected and their antifungal activities against six agricultural plant pathogens were determined. Combined with transcriptomics tools, the mechanism of action of compound A49 (2-chloro-5-trifluoromethoxybenzeneboronic acid) against Botrytis cinerea Pers (B. cinerea) was studied. RESULTS: The EC50 values of compounds A24, A25, A30, A31, A36, A41, A49 and B23 against all six fungi were under 10 µg/mL. Compound A49 displayed significant activity against B. cinerea (EC50 = 0.39 µg/mL), which was better than that of commercial fungicide boscalid (EC50 = 0.55 µg/mL). A49 not only inhibited the germination of B. cinerea spores, but also caused abnormal cell morphology, loss of cell membrane integrity, enhanced cell membrane permeability, and accumulation of intracellular reactive oxygen species. Further findings showed that A49 reduced cellular antioxidant activity, and peroxidase and catalase activities. Transcriptomic results indicated that A49 could degrade intracellular redox processes and alter the metabolism of some amino acids. Meanwhile, A49 showed obvious activity in vivo and low cytotoxicity to mammal cells. CONCLUSION: The boron-containing small molecule compounds had high efficiency and broad-spectrum antifungal activities against six plant pathogens, and are expected to be candidate compounds for a new class of antifungal drugs. © 2023 Society of Chemical Industry.
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Antifúngicos , Fungicidas Industriales , Humanos , Antifúngicos/farmacología , Antifúngicos/química , Boro , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Botrytis , Relación Estructura-ActividadRESUMEN
BACKGROUND: The resistance of traditional chemical fungicides to plant pathogenic fungi and the threats to the safety of humans and the environment highlight an urgent need to find safe and efficient alternatives to chemical fungicides. Owing to the wide spectrum of antifungal activities, low persistence and nontoxicity to mammals and aquatic life, essential oils have considerable potential as low-risk pesticides. In this study, the essential oil and the main components of Angelica sinensis (Oliv.) Diels (Danggui) were extracted, analyzed by GC-MS, and evaluated for their antifungal activities against six plant pathogenic fungi. RESULTS: 3-butylidenephthalide (3-BPH) showed the best antifungal activity against Fusarium graminearum with an EC50 value of 14.35 µg mL-1 . The antifungal mechanistic studies revealed that 3-BPH induced the generation of endogenous ROS to cause lipid peroxidation of the cell membrane and inhibited the biosynthesis of ergosterol, thereby causing the cell membrane damaged to exert its fungicidal activity. Significantly, 3-BPH could reduce deoxynivalenol production compared to the control. CONCLUSION: This study demonstrated the potent fungicidal activity of natural phthalide compound 3-BPH and highlighted its potential as an alternative agent to control F. graminearum. © 2023 Society of Chemical Industry.
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Angelica sinensis , Fungicidas Industriales , Fusarium , Aceites Volátiles , Animales , Angelica sinensis/química , Antifúngicos/farmacología , Antifúngicos/química , Hongos , Fungicidas Industriales/farmacología , Mamíferos , PlantasRESUMEN
Quinolizidine alkaloids isolated from various marine and terrestrial animals and plants are primarily composed of lupinine-, matrine-, and sparteine-type alkaloids. Matrine, phenanthroquinolizidines, bis-quinolizidines, and small molecules from amphibian skins are representative compounds of such alkaloids. Quinolizidine alkaloids harbor anticancer, antibacterial, antiinflammatory, antifibrosis, antiviral, and anti-arrhythmia. In this chapter, we comprehensively outline the biological activity and pharmacological action of quinolizidine alkaloids and discuss new avenues toward the discovery of novel and more efficient drugs based on these naturally occurring compounds. It is urgent for basic research and clinical practice to conduct more targeted comprehensive research based on the lead drugs of quinolizidine alkaloids with significant pharmacological activity.
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Alcaloides , Quinolizidinas , Esparteína , Animales , Alcaloides de Quinolizidina , Alcaloides/farmacología , Quinolizidinas/farmacología , Antiinflamatorios , MatrinasRESUMEN
Epidemic diseases of crops caused by fungi deeply affected the course of human history and processed a major restriction on social and economic development. However, with the enormous misuse of existing antimicrobial drugs, an increasing number of fungi have developed serious resistance to them, making the diseases caused by pathogenic fungi even more challenging to control. Drug repurposing is an attractive alternative, it requires less time and investment in the drug development process than traditional R&D strategies. In this work, we screened 600 existing commercially available drugs, some of which had previously unknown activity against pathogenic fungi. From the primary screen at a fixed concentration of 100 µg/mL, 120, 162, 167, 85, 102, and 82 drugs were found to be effective against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, Phytophthora capsici, Fusarium graminearum and Fusarium oxysporum, respectively. They were divided into nine groups lead compounds, including quinoline alkaloids, benzimidazoles/carbamate esters, azoles, isothiazoles, pyrimidines, pyridines, piperidines/piperazines, ionic liquids and miscellaneous group, and simple structure-activity relationship analysis was carried out. Comparison with fungicides to identify the most promising drugs or lead structures for the development of new antifungal agents in agriculture.
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Antiinfecciosos , Fungicidas Industriales , Fusarium , Humanos , Fungicidas Industriales/química , Reposicionamiento de Medicamentos , Antifúngicos/farmacología , Relación Estructura-Actividad , Antiinfecciosos/farmacologíaRESUMEN
A series of quinoline derivatives were designed and synthesized by the structural simplification of cryptolepine and evaluated for their fungicidal activity against six phytopathogenic fungi. Most of these compounds exhibited remarkable activities against Botrytis cinereain vitro. Among them, compounds A18 and L01 showed superior antifungal activity. Significantly, compared to cryptolepine, compound A18 exhibited broad-spectrum inhibitory activities against B. cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Phytophthora capsica, Magnaporthe oryzae, and Fusarium graminearum with the respective EC50 values of 0.249, 1.569, 3.915, 0.505, 0.246, and 4.999 µg/mL. Compound L01 displayed the best antifungal activity against B. cinerea with an EC50 value of 0.156 µg/mL. Preliminary mechanistic studies showed that compound A18 could inhibit spore germination, affect the permeability of the cell membrane, increase the content of reactive oxygen species, and affect the morphology of hyphae and cells. Moreover, compound A18 showed excellent in vivo protective effect against B. cinerea, which was more potent than pyrimethanil and equitant to cryptolepine. These results evidenced that compound A18 displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.
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Fungicidas Industriales , Quinolinas , Antifúngicos/farmacología , Fungicidas Industriales/química , Quinolinas/farmacología , Alcaloides Indólicos/farmacología , Botrytis , Relación Estructura-Actividad , HongosRESUMEN
Phytopathogenic bacteria are a major cause of crop mortality and yield reduction, especially in field cultivation. The lack of effective chemistry agri-bactericides is responsible for challenging field prevention and treatment, prompting the development of long-lasting solutions to prevent, reduce, or manage some of the most devastating plant diseases facing modern agriculture today and in the future. Therefore, there is an urgent need to find lead drugs preventing and treating phytopathogenic bacterial infection. Drug repurposing, a strategy used to identify novel uses for existing approved drugs outside of their original indication, takes less time and investment than Traditional R&D Strategies in the process of drug development. Based on this method, we conduct a screen of 700 chemically diverse and potentially safe drugs against Xanthomonas oryzae PV. oryzae ACCC 11602 (Xoo), Xanthomonas axonopodis PV. citri (Xac), and Pectobacterium atrosepticum ACCC 19901 (Pa). Furthermore, the structure-activity relationship and structural similarity analysis of active drugs classify potent agri-bactericides into 8 lead series: salicylanilides, cationic nitrogen-containing drugs, azole antifungals, N-containing group, hydroxyquinolines, piperazine, kinase inhibitor and miscellaneous groups. MIC values were evaluated as antibacterial activities in this study. Identifying highly active lead compounds from the screening of approved drugs and comparison with the currently applied plant pathogenic bactericide to validate the bactericidal activity of the best candidates and assess if selected molecules or scaffolds lead to develop new antibacterial agents in the future. In conclusion, this study provides a possibility for the development of potent and highly selective agri-bactericides leads.
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Infecciones Bacterianas , Oryza , Xanthomonas , Pruebas de Sensibilidad Microbiana , Reposicionamiento de Medicamentos , Antibacterianos/farmacología , Antibacterianos/química , Enfermedades de las Plantas/microbiología , Oryza/microbiologíaRESUMEN
AIMS: In this study, we synthesized a 10-fluorine-substitution derivative of CPT (Camptothecin) YCJ100 and evaluated its antitumor activity and systemic toxicity. MATERIALS AND METHODS: Determination of in vitro antitumor activity and mechanism of YCJ100 by the MTT assay, Molecular docking, EdU staining, Cell cycle and apoptosis determination, Western blot analysis and Topoisomerase I activity assay. The antitumor effects of YCJ100 were evaluated in primary HCC (hepatocellular carcinoma), ICC (intrahepatic cholangiocarcinoma) mouse models, and pancreatic cancer xenograft models. KEY FINDINGS: YCJ100 showed superior cytotoxic activity compared to Topotecan in SW480, SW1990, Hep3B, HepG2, A549, A2780, HeLa, and QBC cells. YCJ100 blocked the cell cycle in the G2/M phase, inhibited cell proliferation and induced apoptosis in HepG2 and SW1990 cells. Mechanistically, YCJ100 inhibited topoisomerase I activity in both a cell-free system and a cellular system, similar to the mechanism of Topotecan. YCJ100 showed significant antitumor activity and was more potent than Topotecan in primary HCC and ICC mouse models, as well as a xenograft mouse model. Additionally, YCJ100 showed only minor toxicity to the mouse hematopoietic system, liver, and kidney. These findings indicate that YCJ100 has high antitumor activity and low systemic toxicity. SIGNIFICANCE: Our findings demonstrate that YCJ100, as a Topoisomerase I inhibitor, has in vitro and in vitro antitumor activity. This study provides a new lead compound worthy of further preclinical evaluation and potential clinical development.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pancreáticas , Inhibidores de Topoisomerasa I , Topotecan , Animales , Femenino , Humanos , Ratones , Antineoplásicos/farmacología , Camptotecina , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , ADN-Topoisomerasas de Tipo I/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Simulación del Acoplamiento Molecular , Topotecan/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Topoisomerasa I/farmacología , Neoplasias Pancreáticas/tratamiento farmacológicoRESUMEN
The inhibitory effect of tavaborole on the invasion of Botrytis cinerea in grapes and tomatoes, as well as the potential mechanism involved, was discovered in this study. Our findings showed that tavaborole inhibited Botrytis cinerea spore germination and mycelial expansion in vitro and that the control efficiency in vivo on fruit decay was dose-dependent, which was effective in reducing disease severity and maintaining the organoleptic quality of the fruit, such as reducing weight loss and retaining fruit hardness and titratable acid contents during storage. Furthermore, the precise mechanism of action was investigated further. Propidium iodide staining revealed that Botrytis cinerea treated with tavaborole lost membrane integrity. For further validation, cytoplasmic malondialdehyde accumulation and leakage of cytoplasmic constituents were determined. Notably, the inhibitory effect was also dependent on inhibiting the activities of aminoacyl-tRNA synthetases involved in the aminoacyl-tRNA biosynthesis pathway in Botrytis cinerea. The above findings concluded that tavaborole was effective against Botrytis cinerea infection in postharvest fruit, and a related mechanism was also discussed, which may provide references for the drug repurposing of tavaborole as a postharvest fungicide.
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Frutas , Fungicidas Industriales , Compuestos de Boro , Botrytis , Compuestos Bicíclicos Heterocíclicos con Puentes , Fungicidas Industriales/farmacología , Ligasas , Malondialdehído , Enfermedades de las Plantas , Propidio/farmacología , ARN de Transferencia/farmacologíaRESUMEN
In this work, a series of derivatives with disulfide bonds containing pyridine, pyrimidine, thiophene, thiazole, benzothiazole, and quinoline were designed and synthesized based on the various biological activities of allicin disulfide bond functional groups. The antimicrobial activities of the target compounds were determined, and the structure-activity relationships were discussed. Among them, compound S8 demonstrated the most potent antifungal activity in vitro against Monilinia fructicola (M. fructicola), with an EC50 value of 5.92 µg/mL. Furthermore, an in vivo bioassay revealed that compound S8 exhibited equivalent curative and higher protective effects as the positive drug thiophanate methyl at a concentration of 200 µg/mL. The preliminary mechanism experiments showed that compound S8 could inhibit the growth of M. fructicola' s hyphae in a time- and concentration-dependent manner, and compound S8 could induce the shrinkage of hyphae, disrupt the integrity of the plasma membrane, and cause the damage and leakage of cell contents. More than that, compound S5 also demonstrated an excellent antibacterial effect on Xanthomonas oryzae (X. oryzae), with a MIC90 value of 1.56 µg/mL, which was superior to the positive control, thiodiazole copper.
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Oryza , Quinolinas , Xanthomonas , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/farmacología , Benzotiazoles/farmacología , Cobre/farmacología , Disulfuros/farmacología , Pruebas de Sensibilidad Microbiana , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Piridinas/farmacología , Pirimidinas/farmacología , Quinolinas/farmacología , Relación Estructura-Actividad , Ácidos Sulfínicos , Tiofanato , Tiofenos/farmacologíaRESUMEN
BACKGROUND: The abuse of chemical fungicides not only leads to toxic residues and resistance in plant pathogenic fungi, but also causes environmental pollution and side effects on in humans and animals. Based on the antifungal activities of berberine, seven different types of berberine derivatives (A1-G1) were synthesized, and their antifungal activities against six plant pathogenic fungi were evaluated (Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Phytophthora capsici, Sclerotinia sclerotiorum, and Magnaporthe oryzae). RESULTS: The results for antifungal activities in vitro showed that berberine derivative E1 displayed good antifungal activity against R. solani with a median effective concentration (EC50 ) of 1.77 µg ml-1 , and berberine derivatives F1 and G1 demonstrated broad-spectrum antifungal activities with EC50 values ranging from 4.43 to 42.23 µg ml-1 against six plant pathogenic fungi. Berberine derivatives (E2-E29, F2-F18, and G2-G9) were further synthesized to investigate the structure-activity relationship (SAR), and compound E20 displayed significant antifungal activity against R. solani with an EC50 value of 0.065 µg ml-1 . Preliminary mechanism studies showed that E20 could cause mycelial shrinkage, cell membrane damage, mitochondrial abnormalities and the accumulation of harmful reactive oxygen species, resulting in cell death in R. solani. Moreover, in vivo experimental results showed that the protective effect of E20 was 97.31% at 5 µg ml-1 , which was better than that of the positive control thifluzamide (50.13% at 5 µg ml-1 ). CONCLUSION: Berberine derivative E20 merits further development as a new drug candidate with selective and excellent antifungal activity against R. solani. © 2022 Society of Chemical Industry.
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Berberina , Fungicidas Industriales , Phytophthora , Antifúngicos/química , Berberina/farmacología , Hongos , Fungicidas Industriales/química , Humanos , Plantas/microbiología , Relación Estructura-ActividadRESUMEN
Six new diterpenoids, blusamiferoids A-F (1-6), including four pimarane-type diterpenoids, one rosane-type diterpenoid (3), and one rearranged abietane-type diterpenoid (6), were isolated from the dry aerial parts of Blumea balsamifera. Their structures were characterized by spectroscopic and computational methods. In particular, the structures of 1 and 4 were confirmed by X-ray crystallography. Compounds 5 and 6 were found to dose-dependently inhibit the production of TNF-α, IL-6, and nitrite oxide, and compound 5 also downregulated NF-κB phosphorylation in lipopolysaccharide (LPS)-induced RAW 264.7 cells.