Design, Synthesis, Antibacterial Evaluation, Three-Dimensional Quantitative Structure–Activity Relationship, and Mechanism of Novel Quinazolinone Derivatives

Abstract

Plant bacterial illnesses are common and cause dramatic damage to agricultural goods all over the world, yet there are few efficient bactericides to alleviate them at present. To discover novel antibacterial agents, two series of quinazolinone derivatives with novel structures were synthesized and their bioactivity against plant bacteria was tested. Combining CoMFA model search and the antibacterial bioactivity assay, D32 was identified as a potent antibacterial inhibitor against Xanthomonas oryzae pv. Oryzae (Xoo), with an EC 50 value of 1.5 μg/mL, much better in inhibitory capacity compared to bismerthiazol (BT) and thiodiazole copper (TC) (31.9 and 74.2 μg/mL). The activities of compound D32 against rice bacterial leaf blight in vivo were 46.7% (protective activities) and 43.9% (curative activities), better than commercial drug thiodiazole copper (29.3% protective activities and 30.6% curative activities). Flow cytometry, proteomics, reactive oxygen species, and key defense enzymes were used to further investigate the relevant mechanisms of action of D32. The identification of D32 as an antibacterial inhibitor and revelation of its recognition mechanism not only open the possibility of developing new therapeutic strategies for treatment of Xoo but also provide clues for elucidation of the acting mechanism of quinazolinone derivative D32, which is a possible clinical candidate worth in-depth study.

Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives

“…The apoptotic effect triggered by W2 was evaluated by flow cytometry (BD FACSCalibur) according to our previous work with some slight modifications. 16,21 Different concentrations of W2 were added to the test tubes containing Xoo bacterial solution and incubated for 13 h. Then 100 μL bacterial solution was taken and the cells were stained with annexin V-FITC (5 μL) (ANNEXIN V-FITC/PI Apoptosis Detection Kit; Solarbio, Beijing, China) for 10 min under dark and RT conditions, followed by PI (10 μL) stained for 5 min. The sample data were analyzed using FLOW JO software.…”

“…Isopropanolamine, meanwhile, plays a crucial role as an active linker and serves as the core pharmacophore in antibacterial drugs. [16][17][18] Drawing inspiration from these principles, a series of novel phenol-piperazine-isopropanolamine compounds (W1-W28), as illustrated in Fig. 2, were intentionally designed and synthesized as potential antibacterial agents.…”

“…The first bactericide marketed for the treatment of powdery mildew, Triforine, 15 also contains this moiety. Isopropanolamine, meanwhile, plays a crucial role as an active linker and serves as the core pharmacophore in antibacterial drugs 16–18 . Drawing inspiration from these principles, a series of novel phenol‐piperazine‐isopropanolamine compounds ( W1 – W28 ), as illustrated in Fig.…”

Visible light-mediated synthesis of quinazolinones from benzyl bromides and 2-aminobenzamides without using any photocatalyst or additive

“…Quinazolinones are nitrogenous bicyclic aromatic molecules and important biologically active nitrogen heterocycles. Their derivatives exhibit a wide range of biological activities, including antibacterial, 1 anticancer, 2 antiviral, 3 antitubercular, 4,5 anticonvulsant, 6 anti-inflammatory, 7 antihypertensive, 8 antitumor, 9,10 and antidiabetic 11 activities. The synthesis of quinazolinones has attracted considerable research interest because of their multiple pharmacological activities.…”

NHC-catalyzed [12+2] reaction of polycyclic arylaldehydes for access to indole derivatives

“…Moreover, some of them showed superior bioactivities (Table 3) to the commercial bismerthiazol (BT) and thiodiazole copper (TC). 13…”