Design, Synthesis and Antibacterial Activity of Novel Pyrimidine‐Containing 4H‐Chromen‐4‐One Derivatives **

A series of pyrimidine‐containing 4H‐chromen‐4‐one derivatives were designed and synthesized by combining bioactive substructures. Preliminary biological activity results showed that most of the compounds displayed significant inhibitory activities in vitro against Xanthomonas axonopodis pv. Citri (X. axonopodis), Xanthomonas oryzae pv. oryzae (X. oryzae) and Ralstonia solanacearum (R. solanacearum). In particular, compound 2‐[(3‐{[5,7‐dimethoxy‐4‐oxo‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐1‐benzopyran‐3‐yl]oxy}propyl)sulfanyl]‐4‐(4‐methylphenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile (4c) demonstrated a good inhibitory effect against X. axonopodis and X. oryzae, with the half‐maximal effective concentration (EC50) values of 15.5 and 14.9 μg/mL, respectively, and compound 2‐[(3‐{[5,7‐Dimethoxy‐4‐oxo‐2‐(3,4,5‐trimethoxyphenyl)‐4H‐1‐benzopyran‐3‐yl]oxy}propyl)sulfanyl]‐4‐(3‐fluorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile (4h) showed the best antibacterial activity against R. solanacearum with an EC50 value of 14.7 μg/mL. These results were better than commercial reagents bismerthiazol (BT, 51.7, 70.1 and 52.7 μg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 μg/mL, respectively). In vivo antibacterial activity results indicated that compound 4c displayed better curative (42.4 %) and protective (49.2 %) activities for rice bacterial leaf blight than BT (35.2, 39.1 %) and TC (30.8, 27.3 %). The mechanism of compound 4c against X. oryzae was analyzed through scanning electron microscopy (SEM). These results indicated that pyrimidine‐containing 4H‐chromen‐4‐one derivatives have important value in the research of new agrochemicals.

[1]  Z. Kilic-Kurt,et al.  Synthesis and anticancer activity of some pyrimidine derivatives with aryl urea moieties as apoptosis-inducing agents. , 2020, Bioorganic chemistry.

[2]  Liwei Liu,et al.  Antibacterial activities of novel dithiocarbamate-containing 4H-chromen-4-one derivatives. , 2020, Journal of agricultural and food chemistry.

[3]  Wei Xue,et al.  Synthesis, Biological Activity and Action Mechanism Study of Novel Chalcone Derivatives Containing Malonate , 2020, Chemistry & biodiversity.

[4]  Wei Xue,et al.  Synthesis and antiviral activity of novel myricetin derivatives containing ferulic acid amide scaffolds , 2020 .

[5]  Jiang Shichun,et al.  Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds , 2020, PeerJ Organic Chemistry.

[6]  Liwei Liu,et al.  Design, synthesis and antibacterial activities against Xanthomonas oryzae pv. oryzae, Xanthomonas axonopodis pv. Citri and Ralstonia solanacearum of novel myricetin derivatives containing sulfonamide moiety. , 2019, Pest management science.

[7]  Tian-Yi Zhang,et al.  Synthesis and molecular docking studies of novel pyrimidine derivatives as potential antibacterial agents , 2019, Molecular Diversity.

[8]  Wei Xue,et al.  Synthesis, antiviral and antibacterial activities and action mechanism of penta-1,4-dien-3-one oxime ether derivatives containing a quinoxaline moiety , 2019, New Journal of Chemistry.

[9]  Xufeng Sun,et al.  Design, Synthesis, and Structure-Activity Relationship of New Arylpyrazole Pyrimidine Ether Derivatives As Fungicides. , 2019, Journal of agricultural and food chemistry.

[10]  Xiangyang Li,et al.  Biological activity evaluation and action mechanism of chalcone derivatives containing thiophene sulfonate , 2019, RSC advances.

[11]  Liwei Liu,et al.  Synthesis and antibacterial and antiviral activities of myricetin derivatives containing a 1,2,4-triazole Schiff base , 2019, RSC advances.

[12]  Dan Zeng,et al.  Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases. , 2019, Journal of agricultural and food chemistry.

[13]  Wei Xue,et al.  Novel chalcone derivatives containing a 1,2,4-triazine moiety: design, synthesis, antibacterial and antiviral activities , 2019, RSC advances.

[14]  A. Soliman,et al.  Synthesis and anticancer evaluation of some novel N , O , S heterocyclic compounds pendant to 3‐methyl‐5‐cyano‐6‐(3,4‐dimethoxyphenyl)pyrimidine and other related fused pyrimidines , 2019 .

[15]  Wei Xue,et al.  Design, Synthesis, and Biological Activity of Novel Myricetin Derivatives Containing Amide, Thioether, and 1,3,4-Thiadiazole Moieties , 2018, Molecules.

[16]  E. De Clercq,et al.  Design, synthesis, and antiviral evaluation of novel hydrazone‐substituted thiophene[3,2‐d]pyrimidine derivatives as potent human immunodeficiency virus‐1 inhibitors , 2018, Chemical biology & drug design.

[17]  Jingli Liu,et al.  Design, Synthesis, and Antifungal Activities of Novel 1,2,4‐Triazole Schiff Base Derivatives , 2018, Chemistry & biodiversity.

[18]  A. S. Al-Bogami,et al.  Green Synthesis, Antimicrobial Activity and Cytotoxicity of Novel Fused Pyrimidine Derivatives Possessing a Trifluoromethyl Moiety , 2018, ChemistrySelect.

[19]  Qiong Chen,et al.  Design, Synthesis, and Herbicidal Activity of Pyrimidine-Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors. , 2018, Journal of agricultural and food chemistry.

[20]  B. Song,et al.  Novel bisthioether derivatives containing a 1,3,4-oxadiazole moiety: design, synthesis, antibacterial and nematocidal activities. , 2018, Pest management science.

[21]  Wei Xue,et al.  Synthesis and biological activity of myricetin derivatives containing 1,3,4-thiadiazole scaffold , 2017, Chemistry Central Journal.

[22]  Xinhui Zhang,et al.  LPE‐1, an orally active pyrimidine derivative, inhibits growth and mobility of human esophageal cancers by targeting LSD1 , 2017, Pharmacological research.

[23]  Jun Sik Lee,et al.  Anti-cancer activity of myricetin against human papillary thyroid cancer cells involves mitochondrial dysfunction-mediated apoptosis. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[24]  D. Wedge,et al.  Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti. , 2017, Pest management science.

[25]  黄瑶,et al.  Theoretical Investigation on the Relationship between the Structures and Antioxidant Activities of Myricetin and Dihydromyricetin , 2017 .

[26]  Bang-Cheng Tang,et al.  Synthesis and antibacterial evaluation of novel Schiff base derivatives containing 4(3H)-quinazolinone moiety , 2016, Chemical Papers.

[27]  B. Song,et al.  Antiviral and Antibacterial Activities of N‐(4‐Substituted phenyl) Acetamide Derivatives Bearing 1,3,4‐Oxadiazole Moiety , 2016 .

[28]  Jin-Ming Gao,et al.  Synthesis of pyrazolo[1,5-a]pyrimidine derivatives and their antifungal activities against phytopathogenic fungi in vitro , 2016, Molecular Diversity.

[29]  A. Thakur,et al.  A one pot, two-step synthesis of 5-arylpyrrolo[2,3-d]pyrimidines and screening of their preliminary antibacterial properties. , 2016, Bioorganic & medicinal chemistry letters.

[30]  Guoqiang Zhao,et al.  Myricetin inhibits proliferation and induces apoptosis and cell cycle arrest in gastric cancer cells , 2015, Molecular and Cellular Biochemistry.

[31]  Wei Xue,et al.  Novel myricetin derivatives: Design, synthesis and anticancer activity. , 2015, European journal of medicinal chemistry.

[32]  Qizheng Yao,et al.  Synthesis and quantitative structure-activity relationship (QSAR) analysis of some novel oxadiazolo[3,4-d]pyrimidine nucleosides derivatives as antiviral agents. , 2015, Bioorganic & medicinal chemistry letters.

[33]  Omprakash Tanwar,et al.  Synthesis, 3D-QSAR and docking studies of pyrimidine nitrile-pyrazoline: a novel class of hybrid antimalarial agents , 2014, Medicinal Chemistry Research.

[34]  A. Ćirić,et al.  Antibacterial and antifungal activities of methanol extract and phenolic compounds from Diospyros virginiana L. , 2014 .

[35]  Song Yu-quan,et al.  Synthesis and acaricidal activity of strobilurin-pyrimidine derivatives , 2014 .

[36]  B. Song,et al.  Synthesis, Antibacterial Activities, and 3D‐QSAR of Sulfone Derivatives Containing 1, 3, 4‐Oxadiazole Moiety , 2013, Chemical biology & drug design.

[37]  B. Song,et al.  Synthesis and bioactivity evaluation of novel arylimines containing a 3-aminoethyl-2-[(p-trifluoromethoxy)anilino]-4(3H)-quinazolinone moiety. , 2013, Journal of agricultural and food chemistry.

[38]  S. Kim,et al.  Flavonoid constituents in the leaves of Myrica rubra sieb. et zucc. with anti-inflammatory activity , 2013, Archives of Pharmacal Research.

[39]  D. D'Souza,et al.  Naturally Occurring Flavonoids Against Human Norovirus Surrogates , 2013, Food and Environmental Virology.

[40]  Yong‐Joo Jeong,et al.  Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13 , 2012, Bioorganic & Medicinal Chemistry Letters.

[41]  F. Hadacek,et al.  Exploration of pro-oxidant and antioxidant activities of the flavonoid myricetin , 2011, Redox report : communications in free radical research.

[42]  Gongyou Chen,et al.  A Non-Marker Mutagenesis Strategy to Generate Poly-hrp Gene Mutants in the Rice Pathogen Xanthomonas oryzae pv. oryzicola , 2011 .

[43]  Z. Jing.  Separation of myricetin and dihydromyricetin in Ampelopsis grossedentata and their inhibition of cadiomyocyte apoptosis , 2008 .