{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:30:47Z","timestamp":1791189047466,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1093,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>Haem oxygenases (HO) are involved in the catalytic breakdown of haem to generate carbon monoxide (CO), iron and biliverdin. It is widely accepted that products of haem catabolism are involved in biological signaling in many physiological processes. Conclusions to most studies in this field have gained support from the judicious use of synthetic metalloporphyrins such as chromium mesoporphyrin (CrMP) to selectively inhibit HO. However, metalloporphyrins have also been found to inhibit other haem\u2010dependent enzymes, such as nitric oxide synthase (NOS), cytochromes P\u2010450 (<jats:italic>CYPs<\/jats:italic>) and soluble guanylyl cyclase (sGC), induce the expression of HO\u20101 or exhibit varied toxic effects.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>To obviate some of these problems, we have been examining non\u2010porphyrin HO inhibitors and the present study describes imidazole\u2013dioxolane compounds with high selectivity for inhibition of HO\u20101 (rat spleen microsomes) compared to HO\u20102 (rat brain microsomes)<jats:italic>in vitro<\/jats:italic>. (2<jats:italic>R<\/jats:italic>,4<jats:italic>R<\/jats:italic>)\u20102\u2010[2\u2010(4\u2010chlorophenyl)ethyl]\u20102\u2010[(1<jats:italic>H<\/jats:italic>\u2010imidazol\u20101\u2010yl)methyl]\u20104\u2010methyl\u20101,3\u2010dioxolane hydrochloride) was identified as the most selective inhibitor with a concentration of 0.6\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>inhibiting HO\u20101(inducible) by 50% compared with 394\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>for HO\u20102 (constitutive).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>These compounds were found to have no effects on the catalytic activities of rat brain NOS and lung sGC, but were potent inhibitors of microsomal<jats:italic>CYP<\/jats:italic>2E1 and<jats:italic>CYP<\/jats:italic>3A1\/3A2 activities.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, we have identified imidazole\u2013dioxolanes that are able to inhibit microsomal HO<jats:italic>in vitro<\/jats:italic>with high selectivity for HO\u20101 compared to HO\u20102, and little or no effect on the activities of neuronal NOS and sGC. These molecules could be used to facilitate studies on the elucidation of physiological roles of HO\/CO in biological systems.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>147<\/jats:bold>, 307\u2013315. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706555\">10.1038\/sj.bjp.0706555<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706555","type":"journal-article","created":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T16:12:20Z","timestamp":1133799140000},"page":"307-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Selectivity of imidazole\u2013dioxolane compounds for<i>in vitro<\/i>inhibition of microsomal haem oxygenase isoforms"],"prefix":"10.1111","volume":"147","author":[{"given":"Robert T","family":"Kinobe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Z","family":"Vlahakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J","family":"Vreman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Brien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter A","family":"Szarek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Nakatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.03.010"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/S0090-9556(24)15048-9","article-title":"Selective inhibition of heme oxygenase, without inhibition of nitric oxide synthase or soluble guanylyl cyclase, by metalloporphyrins at low concentrations","volume":"27","author":"APPLETON S.D.","year":"1999","journal-title":"Drug Metabol. Dispos."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(86)80205-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(95)00006-D"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12823"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1139\/y95-065"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00261-5"},{"key":"e_1_2_7_9_1","first-page":"2058","article-title":"Identification of non\u2010porphyrin inhibitors of heme oxygenase\u20101","volume":"24","author":"DENAGEL D.C.","year":"1998","journal-title":"Neuroscience"},{"key":"e_1_2_7_10_1","first-page":"52","article-title":"Endothelium\u2010dependent and \u2010independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light","volume":"28","author":"FURCHGOTT R.F.","year":"1991","journal-title":"Blood Vessels"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1162\/153535003322556886"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.4.962"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02106294"},{"key":"e_1_2_7_14_1","first-page":"353","article-title":"Differential induction of rat hepatic cytochromes P450 3A1, 3A2, 2B1, 2B2 and 2E1 in response to pyridine treatment","volume":"29","author":"KIM H.","year":"2001","journal-title":"Drug Metab. Dispos."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb05276.x"},{"key":"e_1_2_7_16_1","first-page":"399","article-title":"Hydroxylation of p\u2010nitrophenol by rabbit ethanol\u2010induced P\u2010450 isozyme 3a","volume":"29","author":"KOOP D.R.","year":"1986","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00738.2002"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0922-4106(94)90149-X"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.1.208"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2.10.3290025"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.37.1.517"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199707000-00001"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90060-4"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0550416"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(91)90549-X"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(90)90136-M"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1042\/bj2750159","article-title":"Heterogeneity of haem oxygenase 1 and 2 isoenzymes. Rat and primate transcripts for isoenzyme 2 differ in number and size","volume":"275","author":"TRAKSHEL G.M.","year":"1991","journal-title":"Biochem. J."},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(88)90503-6"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199202000-00022"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00552-9"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.12.075"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-74-3-278"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199302000-00021"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000457630"},{"key":"e_1_2_7_36_1","volume-title":"Current Protocols in Toxicology","author":"VREMAN H.J.","year":"1999"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1139\/y98-126"},{"key":"e_1_2_7_38_1","unstructured":"VREMAN H.J. WONG R.J. STEVENSON D.K.&CLARK J.D.(2002).Azalanstat: a novel heme oxygenase inhibitor. 2nd International Conference on Heme Oxygenase (HO\/CO) and Cellular Stress Response. Catania Italy June 6\u20139 2002."},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00067a022"},{"key":"e_1_2_7_40_1","first-page":"73","article-title":"Metalloporphyrin inhibition of heme oxygenase isozymes","volume":"103","author":"WONG R.J.","year":"2000","journal-title":"Acta Haematol."},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14848"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706555","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706555","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0706555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T05:13:48Z","timestamp":1736140428000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0706555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,2]]}},"alternative-id":["10.1038\/sj.bjp.0706555"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0706555","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}