{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:05:25Z","timestamp":1785330325880,"version":"3.55.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    High blood pressure is a major risk factor of cardiovascular disorders. Experimental models of hypertension play a critical role in elucidating its pathophysiological mechanisms and in evaluating novel therapeutic agents. In this study, a series of benzimidazole\u2010based derivatives (I\u2010 XIIIa\u2010d) were designed and synthesized. The structural elucidation of the resulting pyrazoles, pyrimidines, diazepines, and isoxazoles were confirmed and examined against L\u2010NAME induced hypertension in rats\n                    <jats:italic>via<\/jats:italic>\n                    targeting angiotensin II AT1 receptor comparing with Telmisartan as a reference drug. Significant reduction in systolic and diastolic blood pressure were observed upon treatment with VI, XIIIa, and XIIId compounds. Additionally, these compounds modulated the key signaling pathways involved in vascular remodeling, oxidative stress, and apoptosis by restoration of survival kinase signaling (Akt\/GSK3\u03b2), enhancement of anti\u2010apoptotic and anti\u2010inflammatory regulators (BCL2, PPAR\u03b3), modulation of angiotensin receptor balance (AT1\/ AT2), and attenuation of myocardial damage markers (CPK, LDH). The molecular docking showed that compounds VI, XIIIa, and XIIId had the strongest binding affinity against Ang II AT1 receptor. In conclusion, these findings suggest that the structural modifications of benzimidazole core can yield potent antihypertensive agents\n                    <jats:italic>via<\/jats:italic>\n                    a multi\u2010mechanistic mode of action. They also emerge as promising candidates for further pharmacological development in hypertension treatment and cardiovascular complications.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71455","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T19:02:36Z","timestamp":1783364556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Molecular Docking of Benzimidazole Derivatives as Angiotensin II AT1\u2010Receptor Antagonists in a Hypertensive Rat Models"],"prefix":"10.1002","volume":"23","author":[{"given":"Alaadin E.","family":"Sarhan","sequence":"first","affiliation":[{"name":"Department of Therapeutic Chemistry National Research Centre  Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa S.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry National Research Centre  Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6100-6498","authenticated-orcid":false,"given":"Mohamed F.","family":"Abdelhameed","sequence":"additional","affiliation":[{"name":"Pharmacology Department National Research Centre  Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Animal Reproduction and Artificial Insemination National Research Centre  Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-6251","authenticated-orcid":false,"given":"Marwan","family":"Abdelbaset","sequence":"additional","affiliation":[{"name":"Pharmacology Department National Research Centre  Dokki Cairo Egypt"},{"name":"Stark Neurosciences Research Institute School of Medicine, Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal A.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry National Research Centre  Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145481"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47070501"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/vetsci12080777"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145481"},{"key":"e_1_2_13_6_1","article-title":"The Protective Arm of the Renin\u2013Angiotensin System: Functional Roles of AT2 Receptor","volume":"163","author":"Sumners C.","year":"2021","journal-title":"Pharmacological Research"},{"issue":"7","key":"e_1_2_13_7_1","first-page":"456","article-title":"AT2 Receptor Agonists: Therapeutic Potential In Cardiovascular And Renal Diseases","volume":"19","author":"Sumners C.","year":"2022","journal-title":"Nature Reviews Cardiology"},{"issue":"2","key":"e_1_2_13_8_1","first-page":"F181","article-title":"Macrophage Angiotensin AT2 Receptor Activation Is Protective Against Early Phases of LPS\u2010induced Acute Kidney Injury","volume":"325","author":"Fatima N.","year":"2023","journal-title":"American Journal of Physiology. 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