RESUMEN
A series of novel quinazolinone derivatives (E1-E31) containing the 1,2,4-triazole Schiff base moiety and an isopropanol linker were designed, synthesized and assessed as antimicrobial agents in agriculture. All the target compounds were fully characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry (HRMS). Among them, the structure of compound E12 was further confirmed via single crystal X-ray diffraction method. The experimental results indicated that many compounds displayed good in vitro antibacterial efficacies against the tested phytopathogenic bacteria including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Ralstonia solanacearum (Rs). For example, compounds E3, E4, E10, E13, and E22 had EC50 (half-maximal effective concentration) values of 55.4, 39.5, 49.5, 53.5, and 57.4 µg/mL against Xoo, respectively, superior to the commercialized bactericide Bismerthiazol (94.5 µg/mL). In addition, the antibacterial efficacies of compounds E10 and E13 against Xac were about two times more effective than control Bismerthiazol, in terms of their EC50 values. Last, the antifungal assays showed that compounds E22 and E30 had the inhibition rates of 52.7% and 54.6% at 50 µg/mL against Gibberella zeae, respectively, higher than the commercialized fungicide Hymexazol (48.4%).
RESUMEN
A total of 29 novel quinazoline-2-aminothiazole hybrids containing a 4-piperidinylamide linker were designed, synthesized, and evaluated for their anti-microbial properties against phytopathogenic fungi and bacteria of agricultural importance. The anti-fungal assays indicated that some of the target compounds exhibited excellent inhibitory effects in vitro against Rhizoctonia solani. For example, 11 compounds within this series (including 4a, 4g, 4h, 4j, 4o, 4s, 4t, 4u, 4v, 4y, and 4b') were found to possess EC50 values (effective concentration for 50% activity) ranging from 0.42 to 2.05 µg/mL against this pathogen. In particular, compound 4y with a 2-chloro-6-fluorophenyl substituent displayed a potent anti-R. solani efficacy with EC50 = 0.42 µg/mL, nearly threefold more effective than the commercialized fungicide Chlorothalonil (EC50 = 1.20 µg/mL) and also slightly superior to the other fungicide Carbendazim (EC50 = 0.53 µg/mL). Moreover, compound 4y could efficiently inhibit the growth of R. solani in vivo on the potted rice plants, displaying an impressive protection efficacy of 82.3% at 200 µg/mL, better than those of the fungicides Carbendazim (69.8%) and Chlorothalonil (48.9%). Finally, the mechanistic studies showed that compound 4y exerted its anti-fungal effects by altering the mycelial morphology, increasing the cell membrane permeability, and destroying the cell membrane integrity. On the other hand, some compounds demonstrated good anti-bacterial effects in vitro against Xanthomonas oryzae pv. oryzae (Xoo). Overall, the presented results implied that 4-piperidinylamide-bridged quinazoline-2-aminothiazole hybrids held the promise of acting as lead compounds for developing more efficient fungicides to control R. solani.
Asunto(s)
Fungicidas Industriales , Fungicidas Industriales/metabolismo , Fungicidas Industriales/farmacología , Enfermedades de las Plantas/microbiología , Quinazolinas/farmacología , Rhizoctonia , Relación Estructura-Actividad , TiazolesRESUMEN
A total of 52 novel 1,2,4-triazole thioether and thiazolo[3,2-b]-1,2,4-triazole derivatives bearing the 6-fluoroquinazolinyl moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture based on the molecular hybridization strategy. Among them, molecular structures of compounds 5g and 6m were further confirmed via the single-crystal X-ray diffraction method. The bioassay results indicated that some of the target compounds possessed excellent antibacterial activities in vitro against the pathogen Xanthomonas oryzae pv. oryzae (Xoo). For example, compound 6u demonstrated a strong anti-Xoo efficacy with an EC50 value of 18.8 µg/mL, nearly 5-fold more active than that of the commercialized bismerthiazol (EC50 = 93.6 µg/mL). Moreover, the anti-Xoo mechanistic studies revealed that compound 6u exerted its antibacterial effects by increasing the permeability of bacterial membrane, reducing the content of extracellular polysaccharide, and inducing morphological changes of bacterial cells. Importantly, in vivo assays revealed its pronounced protection and curative effects against rice bacterial blight, proving its potential as a promising bactericide candidate for controlling Xoo. Moreover, compound 6u had a good pesticide-likeness based on Tice's criteria. More interestingly, compound 6u with high anti-Xoo activity also demonstrated a potent inhibitory effect of 80.8% against the fungus Rhizoctonia solani at 50 µg/mL, comparable to that of the commercialized chlorothalonil (85.9%). Overall, the current study will provide useful guidance for the rational design of more efficient agricultural antimicrobial agents using the thiazolo[3,2-b]-1,2,4-triazole derivatives bearing the 6-fluoroquinazolinyl moiety as lead compounds.
Asunto(s)
Oryza , Xanthomonas , Antibacterianos/farmacología , Antifúngicos/farmacología , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas , Relación Estructura-Actividad , Sulfuros/farmacología , TriazolesRESUMEN
A series of novel 1,2,4-triazolo[1,5-a]pyrimidine-containing quinazolin-4(3H)-one derivatives (8a-8o) were designed, synthesized and assessed for their in vitro antibacterial and antifungal activities in agriculture. All the title compounds were completely characterized via 1H NMR, 13C NMR, HRMS and IR spectroscopic data. In particular, the molecular structure of compound 8f was further corroborated through a single-crystal X-ray diffraction measurement. The turbidimetric method revealed that some of the compounds displayed noticeable bactericidal potencies against the tested plant pathogenic bacteria. For example, compounds 8m, 8n and 8o possessed higher antibacterial efficacies in vitro against Xanthomonas oryzae pv. oryzae with EC50 values of 69.0, 53.3 and 58.9 µg/mL, respectively, as compared with commercialized agrobactericide bismerthiazol (EC50 = 91.4 µg/mL). Additionally, compound 8m displayed an EC50 value of 71.5 µg/mL toward Xanthomonas axonopodis pv. citri, comparable to control bismerthiazol (EC50 = 60.5 µg/mL). A preliminary structure-activity relationship (SAR) analysis was also conducted, based on the antibacterial results. Finally, some compounds were also found to have a certain antifungal efficacy in vitro at the concentration of 50 µg/mL.
Asunto(s)
Antibacterianos , Antifúngicos , Pirimidinas , Quinazolinonas , Triazoles , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Ascomicetos/efectos de los fármacos , Ascomicetos/crecimiento & desarrollo , Diseño de Fármacos , Fusarium/efectos de los fármacos , Fusarium/crecimiento & desarrollo , Estructura Molecular , Pirimidinas/síntesis química , Pirimidinas/química , Pirimidinas/farmacología , Quinazolinonas/síntesis química , Quinazolinonas/química , Quinazolinonas/farmacología , Ralstonia solanacearum/efectos de los fármacos , Ralstonia solanacearum/crecimiento & desarrollo , Triazoles/síntesis química , Triazoles/química , Triazoles/farmacología , Xanthomonas/efectos de los fármacos , Xanthomonas/crecimiento & desarrolloRESUMEN
A total of 20 1,2,4-triazole Mannich base derivatives bearing the 6-fluoroquinazolinylpiperidinyl moiety were designed, synthesized, and evaluated as antimicrobial agents against phytopathogenic bacteria and fungi according to the molecular hybridization strategy. Of note, the structure of target compound 4h was clearly confirmed through single-crystal X-ray diffraction analysis. The turbidimetric assays indicated that some compounds exhibited excellent antibacterial efficacies in vitro against Xanthomonas oryzae pv. oryzae (Xoo). For example, compounds 4c, 4f, 4j, and 7j had EC50 values of 23.6, 18.8, 23.4, and 24.3 µg/mL, respectively, which were far superior to that of agrobactericide bismerthiazol (EC50 = 92.4 µg/mL). In particular, compound 4f demonstrated a potent anti-Xoo activity approximately five times more active than that of bismerthiazol. Moreover, in vivo assays showed the excellent protective and curative activities of compound 4f against rice bacterial blight, having the potential as an alternative bactericide for controlling Xoo. The structure-activity relationship analysis showed a good pesticide-likeness concerning compound 4f, following Tice's criteria. The anti-Xoo mechanism of compound 4f was preliminarily explored by scanning electron microscopy measurements in living bacteria. Finally, several compounds also exhibited good antifungal activities in vitro against Gibberella zeae at 50 µg/mL. In short, the presented work showed the potential of 6-fluoroquinazolinylpiperidinyl-containing 1,2,4-triazole Mannich base derivatives as effective bactericides for controlling Xoo.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Cloroquina/análogos & derivados , Enfermedades de las Plantas/microbiología , Triazoles/química , Antibacterianos/química , Antifúngicos/química , Cloroquina/química , Cloroquina/farmacología , Diseño de Fármacos , Fusarium/efectos de los fármacos , Fusarium/fisiología , Pruebas de Sensibilidad Microbiana , Oryza/microbiología , Relación Estructura-Actividad , Triazoles/farmacología , Xanthomonas/efectos de los fármacos , Xanthomonas/fisiologíaRESUMEN
A total of 22 quinazoline thioether derivatives incorporating a 1,2,4-triazolo[4,3-a]pyridine moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture. Among these compounds, the chemical structure of compound 6l was further confirmed via single-crystal X-ray diffraction analysis. The bioassay results revealed that some of the compounds possessed noticeable in vitro antibacterial activities against the tested phytopathogenic bacteria. For example, compounds 6b and 6g had EC50 values as low as 10.0 and 24.7 µg/mL against Xanthomonas axonopodis pv. citri (Xac), respectively, which were significantly better than that of the commercial agrobactericide bismerthiazol (56.9 µg/mL). Particularly, compound 6b was also found to be capable of suppressing the pathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo) approximately 12-fold more potent than control bismerthiazol, in terms of their EC50 values (7.2 versus 89.8 µg/mL). Importantly, the most active compound 6b turned out to be one with the highest hydrophilicity and the lowest molecular weight within the series. In vivo bioassays further showed the application prospect of 6b as a promising plant bactericide for controlling Xoo. Additionally, in vitro antifungal activities of these compounds were also evaluated at the concentration of 50 µg/mL. Overall, the present study demonstrated the potential of 1,2,4-triazolo[4,3-a]pyridine-bearing quinazoline thioether derivatives as efficient agricultural antibacterial agents for crop protection.