{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:52:35Z","timestamp":1767192755144,"version":"build-2065373602"},"reference-count":94,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputy for Research and Innovation\u2014Ministry of Education, Kingdom of Saudi Arabia","award":["NU-IF\/INT\/01\/006","118-FMD1-001"],"award-info":[{"award-number":["NU-IF\/INT\/01\/006","118-FMD1-001"]}]},{"name":"Higher Education Commission (HEC) Pakistan","award":["NU-IF\/INT\/01\/006","118-FMD1-001"],"award-info":[{"award-number":["NU-IF\/INT\/01\/006","118-FMD1-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal\/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg\/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg\/kg) for 8 days and 5-FU (150 mg\/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg\/kg I.P. and 10 mg\/kg I.P. for 8 days, followed by 5-FU (150 mg\/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg\/kg and 10 mg\/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered\/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg\/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = \u22127.89 kcal\/mol) with a slight stronger affinity than the calcium channel T-type (S = \u22127.07 kcal\/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.<\/jats:p>","DOI":"10.3390\/molecules27196199","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"6199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects"],"prefix":"10.3390","volume":"27","author":[{"given":"Muhammad Imran","family":"Qayyum","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"},{"name":"Department of Pharmacy, Faculty of Medical and Health Sciences, The University of Poonch, Rawalakot, Azad Jammu & Kashmir 12350, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umer","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-7863","authenticated-orcid":false,"given":"Abdul","family":"Sadiq","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Malakand, Dir (L), Chakdara 18000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Obaidullah","sequence":"additional","affiliation":[{"name":"Department of Agricultural Chemistry and Biochemistry, The University of Agriculture, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mater H.","family":"Mahnashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5498-0687","authenticated-orcid":false,"given":"Osama M.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 55461, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9338-2981","authenticated-orcid":false,"given":"Mohammed M.","family":"Jalal","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-0106","authenticated-orcid":false,"given":"Khalid J.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6632-0646","authenticated-orcid":false,"given":"Ibrahim F.","family":"Halawani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11010-014-2319-5","article-title":"MiR-214 regulates the pathogenesis of patients with coronary artery disease by targeting VEGF","volume":"402","author":"Jin","year":"2015","journal-title":"Mol. 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