Synthesis and biological evaluation of 1,3,4-thiadiazole derivatives as type III secretion system inhibitors against Xanthomonas oryzae

Tao, Hui; Tian, Hao; Jiang, Shan; Xiang, Xuwen; Lin, Yinuo; Ahmed, Wasim; Tang, Ri‐Yuan; Cui, Zi‐Ning

doi:10.1016/j.pestbp.2019.07.005

Cited by 21 publications

(25 citation statements)

References 20 publications

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“…In this study, we extended our previous work − to synthesize a new series of 1,3-thiazole derivatives. We have screened all compounds by using a flow cytometry analysis.…”

Section: Introductionmentioning

confidence: 88%

Novel S-Thiazol-2-yl-furan-2-carbothioate Derivatives as Potential T3SS Inhibitors Against Xanthomonas oryzae on Rice

Jiang

Xiang

et al. 2019

J. Agric. Food Chem.

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Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv oryzae (Xoo) is considered as the most destructive disease of rice. The use of bactericides is among the most widely used traditional methods to control this destructive disease. The excessive and repeated use of the same bactericides is also becoming the reason behind the development of bactericide resistance. The widely used method for finding the new antimicrobial agents often involves the bacterial virulence factors as a target without affecting bacterial growth. Type III secretion system (T3SS) is a protein appendage and is considered as having essential virulence factors in most Gram-negative bacteria. Due to the conserved construct, T3SS has been regarded as an important mark for the blooming of novel antimicrobial drugs. Toward the search of new T3SS inhibitors, an alternative series of 1,3-thiazole derivatives were designed and synthesized. Their structures were characterized and confirmed by 1 H NMR, 13 C NMR, MS, and elemental analysis. All the title compounds inhibited the promoter activity of hpa1 gene significantly. Eight of them showed better inhibition than our previous T3SS inhibitor TS006 (o-coumaric acid, OCA). The treatment of Xoo with eight compounds significantly attenuated HR without affecting bacterial growth. The mRNA levels of some representative genes (hrp/hrc genes) were reduced up to different extents. In vivo bioassay results showed that eight T3SS inhibitors could reduce bacterial leaf blight and bacterial leaf streak symptoms on rice, significantly.

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“…In this study, we extended our previous work − to synthesize a new series of 1,3-thiazole derivatives. We have screened all compounds by using a flow cytometry analysis.…”

Section: Introductionmentioning

confidence: 88%

Novel S-Thiazol-2-yl-furan-2-carbothioate Derivatives as Potential T3SS Inhibitors Against Xanthomonas oryzae on Rice

Jiang

Xiang

et al. 2019

J. Agric. Food Chem.

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“…Plant pathogenic bacteria include Xanthomonas oryzae pv. oryzae (Xoo) , which causes rice bacterial blight with crop yield loss of up to 50% [ 5 , 6 ], and Xanthomonas axonopodis pv . citri (Xac) , which causes citrus canker [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and bioactivity of ferulic acid derivatives containing an β-amino alcohol

Dai

Huang

et al. 2022

BMC Chemistry

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Background Plant diseases caused by viruses and bacteria cause huge economic losses due to the lack of effective control agents. New potential pesticides can be discovered through biomimetic synthesis and structural modification of natural products. A series of ferulic acid derivatives containing an β-amino alcohol were designed and synthesized, and their biological activities were evaluated. Result Bioassays results showed that the EC50 values of compound D24 against Xanthomonas oryzae pv. oryzae (Xoo) was 14.5 μg/mL, which was better than that of bismerthiazol (BT, EC50 = 16.2 μg/mL) and thiodiazole copper (TC, EC50 = 44.5 μg/mL). The in vivo curative and protective activities of compound D24 against Xoo were 50.5% and 50.1%, respectively. The inactivation activities of compounds D2, D3 and D4 against tobacco mosaic virus (TMV) at 500 μg/mL were 89.1, 93.7 and 89.5%, respectively, superior to ningnanmycin (93.2%) and ribavirin (73.5%). In particular, the EC50 value of compound D3 was 38.1 μg/mL, and its molecular docking results showed that compound D3 had a strong affinity for TMV-CP with a binding energy of − 7.54 kcal/mol, which was superior to that of ningnanmycin (− 6.88 kcal /mol). Conclusions The preliminary mechanism research results indicated that compound D3 may disrupt the three-dimensional structure of the TMV coat protein, making TMV particles unable to self-assemble, which may provide potential lead compounds for the discovery of novel plant antiviral agents. Graphical Abstract

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“…Moreover, these systems are conserved in a variety of gram-negative bacteria [ 15 ]. Previous studies that showed small molecules could inhibit T3SS functions in gram-negative bacteria [ 16 – 19 ]. Some small molecules prevent the secretion of the effector protein from Yersinia pestis ( Y. pestis ) into bacterial medium and mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

A small molecule, C24H17ClN4O2S, inhibits the function of the type III secretion system in Salmonella Typhimurium

Boonyom

Roytrakul

Thinwang

2022

Journal of Genetic Engineering and Biotechnology

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Background Salmonella enterica serovar Typhimurium (S. Typhimurium) causes gastroenteritis and diarrhea in humans and food-producing animals. The type III secretion system (T3SS) has been known to be a potent virulence mechanism by injecting effector proteins into the cytosol of host cells. S. Typhimurium encodes two T3SSs by Salmonella pathogenicity islands 1 and 2. Previous studies showed that T3SS shared a potent virulence mechanism and molecular structure among several gram-negative bacteria. Therefore, T3SS has been identified as an attractive target in the development of novel therapeutics for the treatment of bacterial infections. Several studies reported that small-molecule compounds are able to inhibit functions of bacterial T3SSs. A small molecule, C24H17ClN4O2S, has been shown the ability to inhibit the activity of Yersinia pestis T3SS ATPase, YscN, resulting to block the secretion of effector proteins. In this study, we studied the effects and mechanism for SPI-1 T3SS inhibition of this compound in S. Typhimurium. Results We demonstrated that this compound prohibited the secretion of effector proteins from Salmonella via SPI-1 T3SS at 100 μM. As the result, bacterial invasion ability into epithelial cell cultures was reduced. In contrast with previous study, the C24H17ClN4O2S molecule did not inactivate the activity of SPI-1 T3SS ATPase, InvC, in Salmonella. However, we studied the global cellular effects of S. Typhimurium after being treated with this compound using a quantitative proteomic technique. These proteomic results showed that the main SPI-1 transcription regulator, InvF, and two effector proteins, SipA and SipC, were reduced in bacterial cells treated with the compound. Conclusions It may explain that action of the small-molecule compound, C24H17ClN4O2S, for blocking the secretion of SPI-1 T3SS in Salmonella is through inhibition of SPI-1 regulator, InvF, expression. Further studies are necessary to identify specific mechanisms for inhibition between this small-compound and InvF SPI-1 regulator protein.

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Synthesis and biological evaluation of 1,3,4-thiadiazole derivatives as type III secretion system inhibitors against Xanthomonas oryzae

Cited by 21 publications

References 20 publications

Novel S-Thiazol-2-yl-furan-2-carbothioate Derivatives as Potential T3SS Inhibitors Against Xanthomonas oryzae on Rice

Novel S-Thiazol-2-yl-furan-2-carbothioate Derivatives as Potential T3SS Inhibitors Against Xanthomonas oryzae on Rice

Design, synthesis, and bioactivity of ferulic acid derivatives containing an β-amino alcohol

A small molecule, C24H17ClN4O2S, inhibits the function of the type III secretion system in Salmonella Typhimurium

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