{"id":"https://openalex.org/W3023595131","doi":null,"title":"Synthesis of Novel CYP1 Activated Heterocyclic Anticancer Prodrugs","display_name":"Synthesis of Novel CYP1 Activated Heterocyclic Anticancer Prodrugs","publication_year":2011,"publication_date":"2011-04-01","ids":{"openalex":"https://openalex.org/W3023595131","mag":"3023595131"},"language":"en","primary_location":{"id":"pmh:oai:dora.dmu.ac.uk:2086/19500","doi":null,"is_oa":false,"landing_page_url":"https://dora.dmu.ac.uk/bitstreams/5272ec76-115b-4ed1-b257-12db2b660ca3/download","pdf_url":null,"source":{"id":"https://openalex.org/S4306400394","display_name":"DMU Open Research Archive (De Montfort University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I66943878","host_organization_name":"De Montfort University","host_organization_lineage":["https://openalex.org/I66943878"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis or dissertation"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5014942891","display_name":"Avninder S. Bhambra","orcid":"https://orcid.org/0000-0001-7673-4797","observed_orcids":["https://orcid.org/0000-0001-7673-4797"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Avninder S. Bhambra","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-7673-4797","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5014942891"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.9980000257492065,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.0005000000237487257,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13023","display_name":"Synthesis of Organic Compounds","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/anticancer-prodrugs","display_name":"anticancer prodrugs","score":0.9449999928474426},{"id":"https://openalex.org/keywords/cyp1a1","display_name":"CYP1A1","score":0.8500000238418579},{"id":"https://openalex.org/keywords/cyp1b1","display_name":"CYP1B1","score":0.9990000128746033},{"id":"https://openalex.org/keywords/cytochrome-p450-activation","display_name":"cytochrome P450 activation","score":0.8339999914169312},{"id":"https://openalex.org/keywords/chalcones","display_name":"chalcones","score":0.8059999942779541},{"id":"https://openalex.org/keywords/photoisomerization","display_name":"photoisomerization","score":0.8790000081062317},{"id":"https://openalex.org/keywords/pyrimidine-heterocycles","display_name":"pyrimidine heterocycles","score":0.7559999823570251},{"id":"https://openalex.org/keywords/mda-mb-468-cells","display_name":"MDA-MB-468","score":0.7170000076293945},{"id":"https://openalex.org/keywords/mcf-7-cells","display_name":"MCF-7 cells","score":0.9580000042915344},{"id":"https://openalex.org/keywords/cytotoxicity-screening","display_name":"cytotoxicity screening","score":0.7329999804496765}],"concepts":[{"id":"https://openalex.org/C108215921","wikidata":"https://www.wikidata.org/wiki/Q603741","display_name":"Prodrug","level":2,"score":0.8258640766143799},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.46359649300575256},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.40419459342956543},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.37786078453063965},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2638540267944336},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2600674629211426}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:dora.dmu.ac.uk:2086/19500","doi":null,"is_oa":false,"landing_page_url":"https://dora.dmu.ac.uk/bitstreams/5272ec76-115b-4ed1-b257-12db2b660ca3/download","pdf_url":null,"source":{"id":"https://openalex.org/S4306400394","display_name":"DMU Open Research Archive (De Montfort University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I66943878","host_organization_name":"De Montfort University","host_organization_lineage":["https://openalex.org/I66943878"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Thesis or dissertation"},{"id":"mag:3023595131","doi":null,"is_oa":false,"landing_page_url":"https://dora.dmu.ac.uk/handle/2086/19500","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.6240000128746033,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":190,"referenced_works":["https://openalex.org/W112774913","https://openalex.org/W133273011","https://openalex.org/W406537343","https://openalex.org/W611396361","https://openalex.org/W1499177907","https://openalex.org/W1505828315","https://openalex.org/W1559451312","https://openalex.org/W1706348531","https://openalex.org/W1910113143","https://openalex.org/W1918014554","https://openalex.org/W1919851123","https://openalex.org/W1931116526","https://openalex.org/W1942690536","https://openalex.org/W1964137942","https://openalex.org/W1964580006","https://openalex.org/W1964706227","https://openalex.org/W1965134354","https://openalex.org/W1965896778","https://openalex.org/W1967996141","https://openalex.org/W1971079672","https://openalex.org/W1971859935","https://openalex.org/W1972593924","https://openalex.org/W1974313840","https://openalex.org/W1974327959","https://openalex.org/W1975912794","https://openalex.org/W1978217933","https://openalex.org/W1978346197","https://openalex.org/W1979040428","https://openalex.org/W1981398318","https://openalex.org/W1983338915","https://openalex.org/W1984486688","https://openalex.org/W1985382224","https://openalex.org/W1985494972","https://openalex.org/W1986442322","https://openalex.org/W1986902003","https://openalex.org/W1987362747","https://openalex.org/W1988549354","https://openalex.org/W1989254456","https://openalex.org/W1990948601","https://openalex.org/W1991303903","https://openalex.org/W1991662292","https://openalex.org/W1991875535","https://openalex.org/W1992545294","https://openalex.org/W1992781385","https://openalex.org/W1994075121","https://openalex.org/W1995496266","https://openalex.org/W1996115357","https://openalex.org/W1996675163","https://openalex.org/W1997205975","https://openalex.org/W2000402778","https://openalex.org/W2000694785","https://openalex.org/W2002312856","https://openalex.org/W2002452996","https://openalex.org/W2004421657","https://openalex.org/W2005876018","https://openalex.org/W2006989376","https://openalex.org/W2008757142","https://openalex.org/W2009220945","https://openalex.org/W2009309012","https://openalex.org/W2009338130","https://openalex.org/W2009928125","https://openalex.org/W2011750349","https://openalex.org/W2012415513","https://openalex.org/W2012786634","https://openalex.org/W2012979748","https://openalex.org/W2014966556","https://openalex.org/W2019378745","https://openalex.org/W2020247473","https://openalex.org/W2020433921","https://openalex.org/W2021505095","https://openalex.org/W2022464703","https://openalex.org/W2022770260","https://openalex.org/W2024206389","https://openalex.org/W2024783151","https://openalex.org/W2025215722","https://openalex.org/W2026089093","https://openalex.org/W2026227369","https://openalex.org/W2027996680","https://openalex.org/W2028929637","https://openalex.org/W2032232794","https://openalex.org/W2036430194","https://openalex.org/W2038093943","https://openalex.org/W2038271952","https://openalex.org/W2038496890","https://openalex.org/W2039026541","https://openalex.org/W2039463732","https://openalex.org/W2039747119","https://openalex.org/W2040742346","https://openalex.org/W2043485992","https://openalex.org/W2045139706","https://openalex.org/W2047742675","https://openalex.org/W2049654926","https://openalex.org/W2052313646","https://openalex.org/W2052802794","https://openalex.org/W2053796208","https://openalex.org/W2053955604","https://openalex.org/W2053996189","https://openalex.org/W2054856055","https://openalex.org/W2057558096","https://openalex.org/W2059250110","https://openalex.org/W2059828267","https://openalex.org/W2062657421","https://openalex.org/W2062719400","https://openalex.org/W2062792190","https://openalex.org/W2063749929","https://openalex.org/W2068153201","https://openalex.org/W2068705865","https://openalex.org/W2069074470","https://openalex.org/W2070564691","https://openalex.org/W2071021262","https://openalex.org/W2071188907","https://openalex.org/W2071204837","https://openalex.org/W2071341892","https://openalex.org/W2071927813","https://openalex.org/W2071936413","https://openalex.org/W2073369590","https://openalex.org/W2073597770","https://openalex.org/W2075903510","https://openalex.org/W2076315300","https://openalex.org/W2077192777","https://openalex.org/W2079299518","https://openalex.org/W2079624009","https://openalex.org/W2079717769","https://openalex.org/W2080031116","https://openalex.org/W2080204564","https://openalex.org/W2081575170","https://openalex.org/W2082242105","https://openalex.org/W2085416202","https://openalex.org/W2086350370","https://openalex.org/W2086932543","https://openalex.org/W2087017252","https://openalex.org/W2087709256","https://openalex.org/W2087793839","https://openalex.org/W2088062399","https://openalex.org/W2089770528","https://openalex.org/W2089777374","https://openalex.org/W2090065149","https://openalex.org/W2090197940","https://openalex.org/W2093979557","https://openalex.org/W2098960013","https://openalex.org/W2100963721","https://openalex.org/W2102724299","https://openalex.org/W2104398672","https://openalex.org/W2105298656","https://openalex.org/W2105328645","https://openalex.org/W2108864552","https://openalex.org/W2112772593","https://openalex.org/W2113126998","https://openalex.org/W2116826087","https://openalex.org/W2116868531","https://openalex.org/W2118527372","https://openalex.org/W2118916738","https://openalex.org/W2123400343","https://openalex.org/W2124078583","https://openalex.org/W2125624761","https://openalex.org/W2126655188","https://openalex.org/W2128362969","https://openalex.org/W2128605357","https://openalex.org/W2130607894","https://openalex.org/W2134491303","https://openalex.org/W2135783745","https://openalex.org/W2136175619","https://openalex.org/W2137823306","https://openalex.org/W2138107646","https://openalex.org/W2138442205","https://openalex.org/W2143592032","https://openalex.org/W2144119834","https://openalex.org/W2144199131","https://openalex.org/W2144486308","https://openalex.org/W2144678450","https://openalex.org/W2147378653","https://openalex.org/W2149584883","https://openalex.org/W2150406132","https://openalex.org/W2151625494","https://openalex.org/W2152342383","https://openalex.org/W2154052817","https://openalex.org/W2154519280","https://openalex.org/W2155635155","https://openalex.org/W2157807503","https://openalex.org/W2164452916","https://openalex.org/W2164455530","https://openalex.org/W2164575900","https://openalex.org/W2165422066","https://openalex.org/W2169195409","https://openalex.org/W2170810978","https://openalex.org/W2172197167","https://openalex.org/W2256501514","https://openalex.org/W2951409137","https://openalex.org/W2951792077","https://openalex.org/W2964702292"],"related_works":["https://openalex.org/W4409636141","https://openalex.org/W2932709371","https://openalex.org/W2215590528","https://openalex.org/W2783005028","https://openalex.org/W7024976972","https://openalex.org/W2950796458","https://openalex.org/W787511418","https://openalex.org/W3100326326","https://openalex.org/W2937861227","https://openalex.org/W7135273868"],"abstract_inverted_index":{"The":[0,68,167,190,208,260,300,327,342,385,556,616,645],"cytochrome":[1],"P450":[2],"superfamily":[3],"of":[4,11,48,106,116,144,185,200,218,255,279,284,310,313,323,354,364,380,395,409,421,443,450,466,473,484,552,563,580,618,658,667,677,687],"enzymes":[5,63,571],"are":[6,80,643],"critical":[7],"in":[8,25,32,36,125,136,237,576],"the":[9,46,86,91,103,107,114,121,158,181,203,222,248,270,292,305,308,311,314,320,324,357,370,398,412,424,440,453,463,476,487,503,513,519,526,530,536,553,561,577,670,680,692],"metabolism":[10,57,584],"endogenous":[12],"and":[13,17,162,213,286,294,317,361,366,372,416,426,480,489,524,605,613,650,663,684,689,694],"exogenous":[14],"substrates.":[15],"CYP1A1":[16,632],"CYP1B1":[18],"have":[19,70],"been":[20,71,718],"found":[21,623],"to":[22,58,73,82,90,109,240,318,331,518,544,598,624,653],"be":[23,625,654],"over-expressed":[24,64],"tumour":[26,66,145,226,321,521,671,715],"cells":[27,296,360,374,415,428,479,491,672,696,716],"whilst":[28,119],"undetected":[29],"or":[30,152],"present":[31],"very":[33],"low":[34],"levels":[35],"corresponding":[37],"normal":[38],"tissue.":[39],"This":[40],"presented":[41],"a":[42,126,142,253,335,435,550,628,704],"novel":[43,705],"target":[44],"for":[45,149,525],"development":[47],"anti-cancer":[49,76],"prodrugs,":[50],"which":[51,172],"would":[52],"remain":[53],"non-toxic":[54],"until":[55],"undergoing":[56],"toxic":[59,93],"species":[60],"by":[61,334],"CYP1":[62,154,176,538,554,570,588,640,706],"at":[65,627],"sites.":[67],"chalcones":[69,108],"shown":[72],"exhibit":[74],"effective":[75],"prodrug":[77,709],"activity,":[78],"but":[79],"labile":[81],"photoisomerisation":[83,117],"reactions":[84,642],"converting":[85],"potent":[87],"trans":[88,127],"isomer":[89],"less":[92],"cis":[94],"isomer.":[95],"Several":[96],"heterocyclic":[97],"ring":[98],"systems":[99],"were":[100,132,157,188,288,329,542,590,621,637],"incorporated":[101],"across":[102],"\u03b1,\u03b2-unsaturated":[104],"moiety":[105],"produce":[110,332,599],"rigid":[111],"structures,":[112],"eliminating":[113],"possibility":[115],"occurring":[118],"maintaining":[120],"substituted":[122,436],"phenyl":[123,441,464],"groups":[124],"like":[128],"geometry.":[129],"Lead":[130],"compounds":[131,497],"identified":[133,652],"using":[134,339,535,586],"an":[135,197,228,238,276,351,392,406,417,447,470,573,655,674],"vitro":[137],"MTT":[138],"screening":[139],"assay":[140],"against":[141,486,669,691],"panel":[143],"cell":[146,165,170,206,273,506],"lines":[147],"characterised":[148],"their":[150,609],"constitutive":[151],"inducible":[153],"expression.":[155],"These":[156],"MDA":[159,163,204,271,358,399,413,454,477,681],"468,":[160],"MCF7":[161,209,293,295,371,373,425,427,488,490,693,695],"231":[164],"lines.":[166],"non-tumour":[168,504],"MCF10A":[169,505,531],"line":[171,274],"has":[173,717],"no":[174],"basal":[175],"expression":[177],"was":[178,235,258,383,510,549,566,648,651],"used":[179],"as":[180,512,639],"control.":[182],"A":[183,378],"library":[184,254,379],"eighteen":[186],"3,5-diarylpyrazoles":[187],"synthesised.":[189,259,384],"lead":[191,261,386,496,515],"pyrazole":[192],"DMU":[193,263,344,388,402,432,444,457,467,508,547,564,581,594,619,659,702],"10107":[194],"(3-(2,3,4-trimethoxyphenyl)-5-(3,4-methylenedioxyphenyl)pyrazole)":[195],"gave":[196,215,391,446,673],"IC50":[198,216,277,282,352,362,393,407,419,448,471,482,675,685],"value":[199,278,353,394,408,420,449,472,676],"8\u03bcM":[201],"towards":[202,269,291,356,369,397,411,423,452,475,502,529,679,714],"468":[205,272,359,400,414,455,478,682],"line.":[207,507],"cells,":[210,683],"TCDD":[211],"induced":[212,297,375,492,697],"non-induced":[214],"values":[217,283,363,483,686],"10\u03bcM":[219,396,422],"each.":[220],"Although":[221],"pyrazoles":[223],"showed":[224,266,347,405,469,559],"plausible":[225],"toxicity,":[227],"investigation":[229,309],"into":[230],"six":[231],"membered":[232,250],"pyrimidine":[233,315,437],"heterocycles":[234],"undertaken":[236],"attempt":[239],"obtain":[241],"enhanced":[242],"cytotoxicities":[243],"than":[244,633],"those":[245],"observed":[246,290,528],"from":[247,304,608],"five":[249],"pyrazoles.":[251],"Therefore,":[252],"fifteen":[256],"2-amino-4,6-diarylpyrimidines":[257,306,328],"amino-pyrimidine":[262],"10212":[264,445,468,509,548,565,595,620,660],"(2-amino-4-(2,4-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)pyrimidine)":[265],"significant":[267,520],"cytotoxicity":[268,562],"with":[275,298,350,376,430,493,631,698,710],"0.01\u03bcM.":[280],"Notable":[281],"0.3\u03bcM":[285],"0.07\u03bcM":[287,355],"also":[289,460,622],"TCDD.":[299,377,431,494,699],"important":[301],"toxicity":[302,349,501,713],"seen":[303],"prompted":[307],"2-position":[312],"ring,":[316],"assess":[319],"toxicities":[322,522],"synthesised":[325,649],"compounds.":[326],"converted":[330],"4,6-diarylpyrimidones":[333],"one-step":[336],"conversion":[337],"reaction":[338],"sodium":[340],"nitrate.":[341],"pyrimidone":[343],"10313":[345],"(4-(2-methoxyphenyl)-6-(3,4-methylenedioxyphenyl)pyrimidin-2-one)":[346],"high":[348,712],"1.8\u03bcM":[365],"0.5\u03bcM":[367],"3":[368],"nine":[381],"2-morpholino-4,6-diarylpyrimidines":[382],"compound":[387,516],"10405":[389],"(4-(2,4-dimethoxyphenyl)-6-(4-methoxyphenyl)-2-morpholinopyrimidine)":[390],"cells.":[401,456,532],"10600":[403],"(4-(2,4-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)-2-dimethylethylenediaminopyrimidine),":[404],"7\u03bcM":[410],"identical":[418],"treated":[429],"10700":[433],"(2-methyl-4-(2,4-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)pyrimidine),":[434],"based":[438,461],"on":[439,462],"substitutions":[442,465],"2.5\u03bcM":[451],"10800":[458],"(4-(2,4-dimethoxyphenyl)-6-(3,4-methylenedioxyphenyl)pyrimidine),":[459],"0.08\u03bcM":[474],"equal":[481],"0.2\u03bcM":[485],"All":[495],"did":[498],"not":[499],"show":[500,545],"selected":[511],"overall":[514],"due":[517],"recorded,":[523],"non-toxicity":[527],"Inhibition":[533],"studies":[534,585],"known":[537],"inhibitor":[539],"\u03b1-naphthoflavone":[540],"(\u03b1-NF)":[541],"conducted":[543],"that":[546,560,593],"substrate":[551],"enzymes.":[555],"resulting":[557],"data":[558],"completely":[567],"eliminated":[568],"suggesting":[569],"play":[572],"activating":[574],"role":[575],"cytotoxic":[578],"effect":[579],"10212.":[582],"LCMS":[583,662],"isolated":[587],"isoforms":[589],"performed":[591],"showing":[592],"is":[596],"metabolised":[597],"four":[600],"metabolites":[601,617],"(M1,":[602],"M2,":[603],"M3":[604],"M4),":[606],"determined":[607],"individual":[610],"retention":[611],"times":[612],"molecular":[614],"masses.":[615],"generated":[626],"greater":[629],"rate":[630],"CYP1B1.":[634],"Metabolite":[635],"structures":[636],"proposed":[638],"enzyme":[641],"known.":[644],"metabolite":[646,657],"M2":[647,668],"authentic":[656],"via":[661],"co-elution":[664],"studies.":[665],"Screening":[666],"0.6\u03bcM":[678,688],"1\u03bcM":[690],"In":[700],"conclusion,":[701],"10212,":[703],"activated":[707],"anticancer":[708],"selective":[711],"identified.":[719]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2020-05-13T00:00:00"}
