Synthesis, X-ray Crystal Structure, and Antimicrobial Studies of New Quinazolin-4(3H)-one Derivatives Containing the 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazole Moiety and 4-Piperidinyl Linker.

A total of 35 new quinazolinone derivatives bearing the 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole scaffold and the 4-piperidinyl linker were designed, prepared, and assessed for their antibacterial and antifungal activities. Among these derivatives, the chemical structure of compound F5 was clearly verified via single-crystal X-ray diffraction analysis. The experimental results revealed that some of the compounds displayed good even excellent inhibitory effects toward the tested phytopathogenic bacteria. For instance, compound F33 was capable of strongly inhibiting Xanthomonas oryzae pv. oryzae (Xoo) in vitro with an EC50 (half-maximal effective concentration) value of 4.1 µg/mL, about 16-fold more effective than the commercialized bactericide bismerthiazol. Significantly, this compound also effectively suppressed the proliferation of Xoo in the potted rice plants, showing a good in vivo protection efficacy of 47.6% at 200 µg/mL. Subsequently, the antibacterial mechanisms of compound F33 were explored by means of different biophysical and biochemical methods. Last, some of the compounds were found to possess relatively good antifungal activities in vitro, like compound F19 against Phytophthora nicotianae (with an inhibition rate of 67.2% at 50 µg/mL). In a word, the current experimental results imply that the 4-piperidinyl-bridged quinazolinone-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives possess potential as lead compounds for developing more efficient anti-Xoo bactericides.

Design, synthesis, and antimicrobial evaluation of 2-aminothiazole derivatives bearing the 4-aminoquinazoline moiety against plant pathogenic bacteria and fungi.

BACKGROUND: To find more effective agricultural antibiotics, a class of new 2-aminothiazole derivatives containing the 4-aminoquinazoline moiety were synthesized and evaluated for their antimicrobial properties against phytopathogenic bacteria and fungi of agricultural importance. RESULTS: All the target compounds were fully characterized by 1 H NMR, 13 C NMR, and high-resolution mass spectrometry. The bioassay results showed that compound F29 with a 2-pyridinyl substituent exhibited an outstanding antibacterial effect against Xanthomonas oryzae pv. oryzicola (Xoc) in vitro, having an half-maximal effective concentration (EC50 ) value as low as 2.0 µg/mL (over 30-fold more effective than the commercialized agrobactericide bismerthiazol, with an EC50 value of 64.3 µg/mL). In addition, compound F8 with a 2-fluorophenyl group demonstrated a good inhibitory activity toward the bacterium Xanthomonas axonopodis pv. citri (Xac), around twofold more active than bismerthiazol in terms of their EC50 values (22.8 versus 71.5 µg/mL). Interestingly, this compound also demonstrated a notable fungicidal effect against Phytophthora parasitica var. nicotianae, with an EC50 value largely comparable with that of the commercialized fungicide carbendazim. Finally, mechanistic studies revealed that compound F29 exerted its antibacterial effects by increasing the permeability of bacterial membranes, reducing the release of extracellular polysaccharides, and triggering morphological changes of bacterial cells. CONCLUSION: Compound F29 has promising potential as a lead compound for developing more efficient bactericides to fight against Xoc. © 2023 Society of Chemical Industry.

Design, synthesis, crystal structure, and antimicrobial activities of new quinazoline derivatives containing both the sulfonate ester and piperidinylamide moieties.

BACKGROUND: To discover more efficient antimicrobial agents in agriculture, a series of new quinazoline derivatives bearing both sulfonate ester and piperidine-4-carboxamide moieties were synthesized and assessed for their antimicrobial effects. RESULTS: All of the target compounds were fully characterized by proton (1 H) nuclear magnetic resonance (NMR), carbon-13 (13 C) NMR, and high-resolution mass spectroscopy (HRMS), and compound III-6 containing a 3-bromophenyl substituent was clearly confirmed via single-crystal X-ray diffraction analysis. The bioassay results indicated that some compounds displayed noticeable inhibitory effects in vitro against Xanthomonas oryzae pv. oryzicola (Xoc). Further measurements of median effective concentration (EC50 ) values showed that compound III-17 bearing a 4-methoxyphenyl group had the best anti-Xoc efficacy (EC50 = 12.4 µg mL-1 ), far better than the commercialized bismerthiazol (77.5 µg mL-1 ). Moreover, this compound also demonstrated good protection and curative activities in vivo against rice bacterial leaf streak caused by Xoc. CONCLUSION: Compound III-17 had a good potential for further development as a new bactericide for controlling Xoc. © 2023 Society of Chemical Industry.

Design, synthesis, crystal structure, and in vitro antibacterial activities of sulfonamide derivatives bearing the 4-aminoquinazoline moiety.

A total of 66 sulfonamide derivatives bearing the 4-aminoquinazoline moiety were designed and synthesized, and their structures were fully characterized by 1H NMR, 13C NMR, and HRMS techniques. Among them, the structures of compounds 5A10 and 5B11 were further confirmed through X-ray single-crystal diffraction analyses. The bioassay results indicated that some of the target compounds displayed higher inhibition activities in vitro against the tested phytopathogenic bacteria. For example, compound 5A26 exhibited a strong anti-Xanthomonas oryzae pv. oryzicola (Xoc) efficacy with an EC50 (half-maximal effective concentration) value of 30.6 µg/mL, over twofold more active than control agent bismerthiazol (BMT). Additionally, compound 5B14 had a good antibacterial effect against the phytopathogen Xanthomonas axonopodis pv. citric (Xac) with EC50 = 34.5 µg/mL, significantly better than control agent BMT (71.5 µg/mL). The anti-Xoc mechanistic studies showed that compound 5A26 exerted its antibacterial efficacy by increasing the permeability of bacterial membrane, decreasing the content of extracellular polysaccharides, and triggering morphological changes of bacterial cells.

Discovery of Novel Quinazoline-2-Aminothiazole Hybrids Containing a 4-Piperidinylamide Linker as Potential Fungicides against the Phytopathogenic Fungus Rhizoctonia solani.

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.

Pollution characteristics of the recent sediments in the Hangzhou section of the Grand Canal, China.

Spatial distribution of heavy metals, arsenic and organic matter in recent sediments in the Hangzhou section of the Grand Canal and their relationships were analyzed. The results showed that the concentrations of heavy metals and organic matters varied widely along the canal, and the average geological accumulation factors decreased in the following orders: organic carbon(2.6), zinc(2.1), cadmium (2.0), copper(1.5), lead(1.1), nitrogen(0.9), mercury (0.8), phosphorus(0.4), arsenic(0.2) and chromium(0). Content of heavy metals and organic carbon in the top 10 cm layer were lower than that of lower layers, except for mercury and organic carbon in the S9 section. Contents of organic carbon in the top 50 cm layer of the mud sediments are significantly higher than those underneath. In the bottom mud layer, there is a concentration peak of the pollutants. In the mud sediments of the canal, cadmium mainly occurred in the Fe and Mn oxide fraction, copper in the organic fraction, lead in the Fe and Mn oxide fraction, and zinc in the carbonate and the Fe and Mn oxide fraction.