{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:29:06Z","timestamp":1787678946072,"version":"build-2784847793"},"reference-count":37,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["ASSAY and Drug Development Technologies"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Alzheimer's disease (AD), a worldwide renowned progressive neurodegenerative disorder, is the most common cause of dementia. There are several studies on the important role of cholesterol metabolism in AD pathogenesis, which indicated that the high concentrations of serum cholesterol increase the risk of AD. Biosynthesis of the plasma cholesterol and other isoprenoids is catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) through the conversion of HMG-CoA to mevalonic acid in mevalonate pathway. Normally, the high level of plasma cholesterol is downregulated by HGMCR inhibition as the result of degradation of LDL, but in abnormal conditions,<\/jats:italic>\n                    for example,\n                    <jats:italic toggle=\"yes\">high blood glucose, the HMGCR over activated resulting in uncontrolled blood cholesterol. Selective HMGCR inhibitor drugs such as statins, which increase the catabolism of plasma LDL and reduce the plasma concentration of cholesterol, have been investigated as a possible treatment for AD. In the present study, we have identified the binding modes of 22 various derivatives of 3-sulfamoylpyrroles 16, prepared via a [3\u2009+\u20092] cycloaddition of a m\u00fcnchnone with a sulfonamide-substituted alkyne, by using efficient biocomputational tools. Out of 22, 5 ligands, with code numbers 5b, 5c, 5d, 5i, and 5j, possessed most absorption, distribution, metabolism, and excretion (ADME) and toxicity profiles in acceptable ranges. Among ligands, 5j (sodium (3R,5R)-7-(3-(N,N-dimethylsulfamoyl)-5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate) could inhibit HMGCR enzyme in inhibitory binding site with affinity value<\/jats:italic>\n                    \u2212\n                    <jats:italic toggle=\"yes\">12.17 kcal\/mol and binding energy<\/jats:italic>\n                    \u2212\n                    <jats:italic toggle=\"yes\">94.10 kcal\/mol through 5 hydrogen bonds. It showed the best ADME and toxicity profiling and higher affinity values than other potent candidate and market drugs such as atorvastatin and rosuvastatin. Therefore, it is suggested for further<\/jats:italic>\n                    in vivo\n                    <jats:italic toggle=\"yes\">investigation, the druggability of 5j and its cholesterol regulatory impact on AD.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1089\/adt.2017.804","type":"journal-article","created":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T14:59:15Z","timestamp":1509116355000},"page":"342-351","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Risk of Late-Onset Alzheimer's Disease by Plasma Cholesterol: Rational\n                    <i>In Silico<\/i>\n                    Drug Investigation of Pyrrole-Based HMG-CoA Reductase Inhibitors"],"prefix":"10.1177","volume":"15","author":[{"given":"Sajad","family":"Shahbazi","sequence":"first","affiliation":[{"name":"Panjab University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Panjab University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Kuanar","sequence":"additional","affiliation":[{"name":"SOA University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dattatreya","family":"Kar","sequence":"additional","affiliation":[{"name":"SOA University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikha","family":"Singh","sequence":"additional","affiliation":[{"name":"SOA University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranbir Chander","family":"Sobti","sequence":"additional","affiliation":[{"name":"Panjab University","place":["India"]},{"name":"Babasaheb Bhimrao Ambedkar University","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39619-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_3_3_4_2","first-page":"79","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"45","author":"Mahley R","year":"1986","unstructured":"Mahley R: Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. 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