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However, the long-term overuse of herbicides can lead to a range of adverse effects. Therefore, it is essential to develop innovative and sustainable herbicides. A series of pyridazinone derivatives targeting phytoene desaturase (PDS) were designed and synthesized by using a structure-based drug design strategy. A bioassay showed that 16c (100%, 85%) exhibited stronger herbicidal activity against portulaca oleracea (P.o.) than that of norflurazon (NRF, 60%, 45%) in both post- and pre-emergence applications at a dosage of 150 g a.i.\/ha, while also showing greater safety to nontarget organisms. Meanwhile, levels of 15-cis-phytoene, carotenoids, and chlorophyll revealed that 16c effectively inhibited PDS activity. Molecular dynamics simulations and binding action assays confirmed that Arg195 is a key residue for the interaction between 16c and Synechococcus PDS (SynPDS). Therefore, 16c could be developed as a potent PDS inhibitor for herbicides.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c01243","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T20:01:37Z","timestamp":1786046497000},"page":"24949-24959","source":"Crossref","is-referenced-by-count":0,"title":["Structure-Based\nRational Design and Synthesis of Pyridazinone\nHerbicides Targeting Phytoene Desaturase"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0378-0589","authenticated-orcid":true,"given":"Chao","family":"Chen","sequence":"first","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, PR China, 550025"]},{"name":"Guizhou Medical University , , Natural Products Research Center of Guizhou Province , ,","place":["Guiyang, PR China, 550014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, PR China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, PR China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4070-0824","authenticated-orcid":true,"given":"Xiuhai","family":"Gan","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , ,","place":["Guiyang, PR China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026081910152752800_cit1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fagro.2019.00003","article-title":"Grand challenges\nin weed management","volume":"1","author":"Chauhan","year":"2020","journal-title":"Front. 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