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In greenhouse pot experiments,\n                      <jats:bold>9i<\/jats:bold>\n                      achieved a control efficacy 4.7 times greater than that of andrographolide. Structure\u2013activity relationship analysis indicated that introducing aromatic substituents containing electron\u2010withdrawing groups at the C3 position significantly improved insecticidal activity. Morphological observations by stereomicroscopy and scanning electron microscopy revealed severe damage to the insect body surface after treatment. Biochemical assays further showed that\n                      <jats:bold>9i<\/jats:bold>\n                      markedly induced the activities of key antioxidant enzymes, including superoxide dismutase and catalase. Toxicological evaluation demonstrated favorable selectivity, with low toxicity toward non\u2010target organisms, including honeybees, mammalian bEND.3 cells, zebrafish larvae, and representative microorganisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Structural optimization substantially enhances the insecticidal activity of andrographolide. Compound\n                      <jats:bold>9i<\/jats:bold>\n                      represents a promising lead candidate for eco\u2010friendly insecticide development and provides a valuable basis for future pesticide discovery. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.71067","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:14:52Z","timestamp":1782447292000},"page":"10261-10271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of natural product\u2010derived pesticide candidates: synthesis, aphicidal activity, and toxicological evaluation of andrographolide derivatives"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3569-0251","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Life 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