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In the present study, a new strain of <jats:italic>Chaetomium globosum<\/jats:italic> (KM651986) was investigated resulting in the isolation of two unreported lecanoric acid derivatives <jats:bold>1<\/jats:bold> and <jats:bold>2<\/jats:bold>, for the first time, which were analyzed using spectroscopic methods, SwissSimilarity, and SwissTargetPrediction. Thus, predicting the possible biological targets for <jats:bold>1<\/jats:bold> and <jats:bold>2.<\/jats:bold> Consequently, the crude methanol extract of <jats:italic>C. globosum<\/jats:italic>, compounds <jats:bold>1<\/jats:bold> and <jats:bold>2<\/jats:bold> were investigated for their anti-diabetic activity using streptozocin (STZ) - induced diabetic rat model. Results indicated that the crude extract <jats:italic>C. globosum<\/jats:italic> and compounds <jats:bold>1<\/jats:bold> and <jats:bold>2<\/jats:bold>\u00a0significantly impacted serum glucose, insulin, HbA1c levels, hepatic glucose-6-phosphate dehydrogenase (G6PD) content, cAMP levels, and hepatic \u03b1-amylase content. Compound <jats:bold>2<\/jats:bold> showed a significant decrease in serum glucose by 40% and an increase in insulin level by 65% compared to STZ-diabetic rats, indicating its potent anti-hyperglycemic effect and potential in improving insulin secretion and cell regeneration. Compound <jats:bold>2<\/jats:bold> also elevated hepatic G6PD, normalized cAMP levels, and decreased hepatic \u03b1-amylase, indicating its potential in improving glucose metabolism at the hepatic level. Therefore, compound <jats:bold>2<\/jats:bold> emerges as particularly promising anti-diabetic candidate meriting further investigation into its potential therapeutic mechanisms of action.<\/jats:p>","DOI":"10.1038\/s41598-025-05875-4","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T08:45:49Z","timestamp":1751445949000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Two unreported lecanoric acid derivatives isolated from Chaetomium globosum KM651986 and their anti-diabetic effect"],"prefix":"10.1038","volume":"15","author":[{"given":"Rehab A.","family":"Hussein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enaam M.","family":"AbouZeid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia O.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gehad A. 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