4(3H)-quinazolinone is a functional scaffold that exists widely both in natural products and synthetic organic compounds. Its drug-like derivatives have been extensively synthesized with interesting biological features including anticancer, anti-inflammatory, antiviral, antimalarial, antibacterial, antifungal, and herbicidal, etc. In this review, we highlight the medicinal and agrochemical versatility of the 4(3H)-quinazolinone scaffold according to the studies published in the past six years (2019–2024), and comprehensively give a summary of the target recognition, structure–activity relationship, and mechanism of its analogs. The present review is expected to provide valuable guidance for discovering novel lead compounds containing 4(3H)-quinazolinone moiety in both drug and agrochemical research.

To identify fungicide lead compounds with novel scaffold and high efficacy, a library of 4,5-dihydrotetrazolo [1,5-a]thieno [2,3-e]pyridine derivatives, consisting of 10 newly synthesized compounds and 12 previously reported compounds, was evaluated for their potential as fungicide agents. In vitro bioassay results indicated that some target compounds exhibited certain antifungal activity against the tested fungi at a concentration of 50 μg/mL. Especially, compounds I-1, I-5, I-7, and I-12 demonstrated promising antifungal activity against C. arachidicola, R. solani, and S. sclerotiorum, with EC₅₀ values ranging from 4.61 to 6.66 μg/mL. Additionally, transcriptome analysis revealed that the molecular mode of action of compound I-12 involves the inhibition of nitrogen metabolism and the proteasome pathway. The present work demonstrates that 4,5,6,7-tetrahydrothieno [3,2-b] pyridine represents a promising lead scaffold and provides important theoretical foundations and innovative perspectives for the development of novel and highly efficient fungicides.

To develop aryloxyphenoxypropionate herbicides with novel structure and improved activity, a total of twenty-eight novel quinazolinone–phenoxypropionate derivatives containing a diester moiety were designed and synthesized. The herbicidal bioassay results in the greenhouse showed that QPEP-I-4 exhibited excellent herbicidal activity against E. crusgalli, D. sanguinalis, S. alterniflora, E. indica, and P. alopecuroides with inhibition rates >80% at a dosage of 150 g ha⁻¹ and displayed higher crop safety to G. hirsutum, G. max, and A. hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying the herbicidal mechanism by phenotypic observation, membrane permeability evaluation, and transcriptomic analysis revealed that a growth inhibition of plants by QPPE-I-4 was the result from damage of the plants’ biomembrane. The evaluation of ACCase activity in vivo indicated that QPPE-I-4 could inhibit ACCase and may be a new type of ACCase inhibitor. The present work indicated that QPPE-I-4 could represent a lead compound for further developing novel AOPP herbicides.

In continuation of our efforts to identify novel herbicide lead compounds with enhanced activity, a series of eighteen 5-acylbarbituric acid derivatives containing a pyrimidinedione moiety were designed and synthesized. Their herbicidal activities were subsequently evaluated in the greenhouse. Bioassay results demonstrated that most of the newly synthesized compounds exhibited significant herbicidal efficacy at a dosage of 150 g ha⁻¹, with compounds BA-I-2, BA-II-2, BA-III-2, and BA-III-5 achieving complete inhibition of the tested weeds. Further investigation into the herbicidal spectrum revealed that compounds BA-II-2 and BA-III-2 displayed excellent herbicidal activity against 14 and 13 out of 16 tested weed species, respectively, with inhibition rates exceeding 80% at dosages as low as 18.8 g ha⁻¹. More promisingly, compound BA-III-2 was found to be safe for Triticum aestivum at a dosage of 37.5 g ha⁻¹. Molecular mode of action studies, including phenotypic observations, membrane permeability evaluations, and molecular docking, suggested that BA-III-2 may function as a protoporphyrinogen IX oxidase (PPO) inhibitor. The present work indicates that BA-III-2 holds potential as a PPO-inhibiting herbicide for effective weed control in wheat fields and is expected to provide important theoretical foundations for the development of novel and highly efficient herbicides.

In continuation of our efforts to identify novel herbicide lead compounds, twenty new 5-(1-amino-4-phenoxybutylidene)barbituric acid derivatives containing an enamino diketone motif were synthesized and evaluated for their herbicidal activities. The greenhouse bioassay results indicated that several of the target compounds, including BA-1, BA-2, BA-5, BA-18, and BA-20, exhibited notable post-emergence herbicidal activity, with sum inhibition rates exceeding 70% at a dosage of 150 g ha⁻¹, which was superior to that of the commercial herbicide flumiclorac-pentyl (FP). The structure–activity relationship analysis demonstrated that the steric and electronic effects of the R group, as well as the lipophilicity of the target compounds, significantly influenced herbicidal activity. Among these, BA-1 was identified as a promising herbicide lead compound due to its high total herbicidal efficacy, broad-spectrum activity, and favorable crop safety profile. Molecular simulation studies indicated that BA-1 binds effectively to Nicotiana tabacum protoporphyrinogen IX oxidase (NtPPO), suggesting its potential as a novel PPO inhibitor. This study highlights BA-1 as a promising lead compound for the development of novel PPO-inhibiting herbicides.

To develop aryloxyphenoxypropionate herbicides with novel structure and improved activity, a total of twenty-eight novel quinazolinone–phenoxypropionate derivatives containing a diester moiety were synthesized and tested for herbicidal activity. The bioassay results in the greenhouse showed that QPEP-I-4 exhibited excellent herbicidal activity against E. crusgalli, D. sanguinalis, S. alterniflora, E. indica, and P. alopecuroides with inhibition rates >80% at a dosage of 150 g ha-1, and displayed higher crop safety to G. hirsutum, G. max, and A. hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying of the molecular mode of action by phenotypic observation, membrane permeability evaluation, and transcriptomic analysis revealed that a growth inhibition of plant by QPPE-I-4 was the result from damage of plants biomembrane. The evaluation of ACCase activity in vivo indicated that QPPE-I-4 could inhibit ACCase and may be a new type of ACCase inhibitor. The present work demonstrated that QPPE-I-4 could serve as a lead compound for further developing novel AOPP herbicides.