{"id":"https://openalex.org/W7225189371","doi":"https://doi.org/10.1080/10406638.2026.2752853","title":"Design, Synthesis and Biological Evaluation of 5-Alkyl[1,2,4]triazino [5,6-b]indole-3-thiol Based Compounds as Potential Histone Deacetylase Inhibitor Candidates","display_name":"Design, Synthesis and Biological Evaluation of 5-Alkyl[1,2,4]triazino [5,6-b]indole-3-thiol Based Compounds as Potential Histone Deacetylase Inhibitor Candidates","publication_year":2026,"publication_date":"2026-11-03","ids":{"openalex":"https://openalex.org/W7225189371","doi":"https://doi.org/10.1080/10406638.2026.2752853"},"language":"en","primary_location":{"id":"doi:10.1080/10406638.2026.2752853","doi":"https://doi.org/10.1080/10406638.2026.2752853","is_oa":false,"landing_page_url":"https://doi.org/10.1080/10406638.2026.2752853","pdf_url":null,"source":{"id":"https://openalex.org/S178924077","display_name":"Polycyclic aromatic compounds","issn_l":"1026-7743","issn":["1026-7743","1040-6638","1563-5333"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-1","norway-1","poland-70","russia-white-list-3"],"host_organization":"https://openalex.org/P4310320547","host_organization_name":"Taylor & Francis","host_organization_lineage":["https://openalex.org/P4310320547","https://openalex.org/P4310320449"],"host_organization_lineage_names":["Taylor & Francis","Informa"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Polycyclic Aromatic Compounds","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"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/A5087480244","display_name":"Ahmad J. Almalki","orcid":"https://orcid.org/0000-0002-1333-980X","observed_orcids":["https://orcid.org/0000-0002-1333-980X"]},"institutions":[{"id":"https://openalex.org/I185163786","display_name":"King Abdulaziz University","ror":"https://ror.org/02ma4wv74","country_code":"SA","type":"education","lineage":["https://openalex.org/I185163786"]}],"countries":["SA"],"is_corresponding":true,"raw_author_name":"Ahmad J. Almalki","raw_affiliation_strings":["Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University","Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University","Toxicology and Forensic Sciences Unit, King Fahd Medical Research Center, King Abdulaziz University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]},{"raw_affiliation_string":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]},{"raw_affiliation_string":"Toxicology and Forensic Sciences Unit, King Fahd Medical Research Center, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088659394","display_name":"Tarek Salah Ibrahim","orcid":"https://orcid.org/0000-0002-3049-4617","observed_orcids":["https://orcid.org/0000-0002-3049-4617"]},"institutions":[{"id":"https://openalex.org/I185163786","display_name":"King Abdulaziz University","ror":"https://ror.org/02ma4wv74","country_code":"SA","type":"education","lineage":["https://openalex.org/I185163786"]}],"countries":["SA"],"is_corresponding":false,"raw_author_name":"Tarek S. Ibrahim","raw_affiliation_strings":["Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University"],"raw_orcid":"https://orcid.org/0000-0002-3049-4617","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005462531","display_name":"Mohammed A. AlAwadh","orcid":"https://orcid.org/0000-0002-1126-5886","observed_orcids":["https://orcid.org/0000-0002-1126-5886"]},"institutions":[{"id":"https://openalex.org/I185163786","display_name":"King Abdulaziz University","ror":"https://ror.org/02ma4wv74","country_code":"SA","type":"education","lineage":["https://openalex.org/I185163786"]}],"countries":["SA"],"is_corresponding":false,"raw_author_name":"Mohammed A. Al-Awadh","raw_affiliation_strings":["Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University","King Fahd Medical Research Center, King Abdulaziz University"],"raw_orcid":"https://orcid.org/0000-0002-1126-5886","affiliations":[{"raw_affiliation_string":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]},{"raw_affiliation_string":"King Fahd Medical Research Center, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025973169","display_name":"Faris Alkhilaiwi","orcid":"https://orcid.org/0000-0002-9902-4787","observed_orcids":["https://orcid.org/0000-0002-9902-4787"]},"institutions":[{"id":"https://openalex.org/I185163786","display_name":"King Abdulaziz University","ror":"https://ror.org/02ma4wv74","country_code":"SA","type":"education","lineage":["https://openalex.org/I185163786"]}],"countries":["SA"],"is_corresponding":false,"raw_author_name":"Faris A. Alkhilaiwi","raw_affiliation_strings":["Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University","Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]},{"raw_affiliation_string":"Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University","institution_ids":["https://openalex.org/I185163786"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5049476900","display_name":"Abdulrahman Salim Alharbi","orcid":"https://orcid.org/0000-0001-9379-2155","observed_orcids":["https://orcid.org/0000-0001-9379-2155"]},"institutions":[{"id":"https://openalex.org/I206935292","display_name":"Shaqra University","ror":"https://ror.org/05hawb687","country_code":"SA","type":"education","lineage":["https://openalex.org/I206935292"]}],"countries":["SA"],"is_corresponding":false,"raw_author_name":"Abdulrahman S. Alharbi","raw_affiliation_strings":["Department of Chemistry, College of Science and Humanities-Dawadmi, Shaqra University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, College of Science and Humanities-Dawadmi, Shaqra University","institution_ids":["https://openalex.org/I206935292"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5087480244"],"corresponding_institution_ids":["https://openalex.org/I185163786"],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.7306433,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"1","last_page":"23"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.9121000170707703,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.9121000170707703,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.05339999869465828,"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/T14099","display_name":"Synthesis and Characterization of Heterocyclic Compounds","score":0.031300000846385956,"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/histone-deacetylase-inhibitors","display_name":"histone deacetylase inhibitors","score":0.9819999933242798},{"id":"https://openalex.org/keywords/antiproliferative-activity","display_name":"antiproliferative activity","score":0.8349999785423279},{"id":"https://openalex.org/keywords/hdac4","display_name":"HDAC4","score":0.9020000100135803},{"id":"https://openalex.org/keywords/hdac6","display_name":"HDAC6","score":1.0},{"id":"https://openalex.org/keywords/hdac8","display_name":"HDAC8","score":1.0},{"id":"https://openalex.org/keywords/n-ethylation","display_name":"N-ethylation","score":0.7120000123977661},{"id":"https://openalex.org/keywords/linker-length","display_name":"linker length","score":0.7760000228881836},{"id":"https://openalex.org/keywords/admet-properties","display_name":"ADMET properties","score":0.6899999976158142},{"id":"https://openalex.org/keywords/anticancer-agents","display_name":"anticancer agents","score":0.6959999799728394},{"id":"https://openalex.org/keywords/induced-fit-docking","display_name":"induced fit docking","score":0.6510000228881836},{"id":"https://openalex.org/keywords/hct116-cells","display_name":"HCT116 cells","score":0.8379999995231628},{"id":"https://openalex.org/keywords/mcf-7-cells","display_name":"MCF-7 cells","score":1.0},{"id":"https://openalex.org/keywords/hepg2-cells","display_name":"HepG2 cells","score":1.0}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.9128000140190125},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.7153000235557556},{"id":"https://openalex.org/C41685203","wikidata":"https://www.wikidata.org/wiki/Q1974042","display_name":"Docking (animal)","level":2,"score":0.6629999876022339},{"id":"https://openalex.org/C2778305200","wikidata":"https://www.wikidata.org/wiki/Q174378","display_name":"Histone deacetylase","level":4,"score":0.6535999774932861},{"id":"https://openalex.org/C25737173","wikidata":"https://www.wikidata.org/wiki/Q18042128","display_name":"HDAC8","level":5,"score":0.6064000129699707},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5554999709129333},{"id":"https://openalex.org/C41847442","wikidata":"https://www.wikidata.org/wiki/Q916723","display_name":"Lipinski's rule of five","level":4,"score":0.4722999930381775},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.4325000047683716},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4300999939441681},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.40860000252723694},{"id":"https://openalex.org/C2777752112","wikidata":"https://www.wikidata.org/wiki/Q903238","display_name":"Lead compound","level":3,"score":0.38179999589920044},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.37689998745918274},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.376800000667572},{"id":"https://openalex.org/C116073593","wikidata":"https://www.wikidata.org/wiki/Q864491","display_name":"Biological activity","level":3,"score":0.3725999891757965},{"id":"https://openalex.org/C2776202225","wikidata":"https://www.wikidata.org/wiki/Q3569101","display_name":"Histone deacetylase inhibitor","level":5,"score":0.3653999865055084},{"id":"https://openalex.org/C2777752497","wikidata":"https://www.wikidata.org/wiki/Q286779","display_name":"IC50","level":3,"score":0.34860000014305115},{"id":"https://openalex.org/C193042331","wikidata":"https://www.wikidata.org/wiki/Q1772003","display_name":"Structure\u2013activity relationship","level":3,"score":0.3434000015258789},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.3375000059604645},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3222000002861023},{"id":"https://openalex.org/C41183919","wikidata":"https://www.wikidata.org/wiki/Q423026","display_name":"Active site","level":3,"score":0.3012000024318695},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.28700000047683716},{"id":"https://openalex.org/C2994372470","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell lines","level":4,"score":0.28679999709129333},{"id":"https://openalex.org/C164126121","wikidata":"https://www.wikidata.org/wiki/Q766383","display_name":"Quantitative structure\u2013activity relationship","level":2,"score":0.28029999136924744},{"id":"https://openalex.org/C69366308","wikidata":"https://www.wikidata.org/wiki/Q2272286","display_name":"ADME","level":3,"score":0.27489998936653137},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.2718999981880188},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.2565000057220459},{"id":"https://openalex.org/C11804247","wikidata":"https://www.wikidata.org/wiki/Q896177","display_name":"Protein\u2013protein interaction","level":2,"score":0.25200000405311584}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1080/10406638.2026.2752853","doi":"https://doi.org/10.1080/10406638.2026.2752853","is_oa":false,"landing_page_url":"https://doi.org/10.1080/10406638.2026.2752853","pdf_url":null,"source":{"id":"https://openalex.org/S178924077","display_name":"Polycyclic aromatic compounds","issn_l":"1026-7743","issn":["1026-7743","1040-6638","1563-5333"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","jufo-1","norway-1","poland-70","russia-white-list-3"],"host_organization":"https://openalex.org/P4310320547","host_organization_name":"Taylor & Francis","host_organization_lineage":["https://openalex.org/P4310320547","https://openalex.org/P4310320449"],"host_organization_lineage_names":["Taylor & Francis","Informa"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Polycyclic Aromatic Compounds","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8371999859809875}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":59,"referenced_works":["https://openalex.org/W137915467","https://openalex.org/W1537435446","https://openalex.org/W1975691556","https://openalex.org/W1979519622","https://openalex.org/W1985588649","https://openalex.org/W1991483463","https://openalex.org/W2008324827","https://openalex.org/W2009423060","https://openalex.org/W2017413126","https://openalex.org/W2031168104","https://openalex.org/W2043124942","https://openalex.org/W2057560174","https://openalex.org/W2078454854","https://openalex.org/W2089709024","https://openalex.org/W2092476693","https://openalex.org/W2102377211","https://openalex.org/W2116068882","https://openalex.org/W2131487381","https://openalex.org/W2135619784","https://openalex.org/W2499955277","https://openalex.org/W2511531422","https://openalex.org/W2522126547","https://openalex.org/W2595118517","https://openalex.org/W2611330792","https://openalex.org/W2624729957","https://openalex.org/W2792323180","https://openalex.org/W2795615449","https://openalex.org/W2825175556","https://openalex.org/W2900781628","https://openalex.org/W2937209531","https://openalex.org/W2944548605","https://openalex.org/W2962526936","https://openalex.org/W2995898384","https://openalex.org/W3004398354","https://openalex.org/W3010399544","https://openalex.org/W3013570186","https://openalex.org/W3014323314","https://openalex.org/W3039786831","https://openalex.org/W3087188501","https://openalex.org/W3092249886","https://openalex.org/W3098596682","https://openalex.org/W3160763916","https://openalex.org/W3164625589","https://openalex.org/W3177448875","https://openalex.org/W3193513064","https://openalex.org/W3212509579","https://openalex.org/W4205148977","https://openalex.org/W4205826924","https://openalex.org/W4225009719","https://openalex.org/W4293769577","https://openalex.org/W4303959017","https://openalex.org/W4311682388","https://openalex.org/W4386314838","https://openalex.org/W4400292936","https://openalex.org/W4401255945","https://openalex.org/W4412173537","https://openalex.org/W4413913372","https://openalex.org/W4414011749","https://openalex.org/W4417332934"],"related_works":["https://openalex.org/W2054654013","https://openalex.org/W3043366878","https://openalex.org/W2940564310","https://openalex.org/W2150377707","https://openalex.org/W2040371498","https://openalex.org/W2978777524","https://openalex.org/W3204775644","https://openalex.org/W4407592030","https://openalex.org/W2803221044","https://openalex.org/W2607008358"],"abstract_inverted_index":{"The":[0],"resilient":[1],"nature":[2],"of":[3,9,16,39,148,154,165],"cancer":[4],"limits":[5],"the":[6,14,117,140,145,151,168,171,174],"long-term":[7],"efficacy":[8],"conventional":[10],"single-target":[11],"chemotherapeutics,":[12],"motivating":[13],"development":[15],"structurally":[17,179],"novel":[18,50],"anticancer":[19,183],"agents":[20],"with":[21,46,73,102,110,121,162,185,190],"potential":[22,71,146,196],"multitarget":[23],"activity.":[24,113],"This":[25],"study":[26],"aimed":[27],"to":[28,44,95,127],"design,":[29],"synthesize,":[30],"and":[31,33,55,65,76,83,87,105,131,181],"biologically":[32],"computationally":[34,186],"evaluate":[35],"a":[36,178,195],"new":[37],"series":[38],"triazinoindole-capped":[40],"acid-hydrazide":[41],"hybrids":[42],"designed":[43],"interact":[45],"histone":[47],"deacetylases.":[48],"Twelve":[49],"compounds":[51],"(6a\u2013l)":[52],"were":[53,78,92],"synthesized":[54],"characterized.":[56],"Their":[57],"antiproliferative":[58,112],"activity":[59,153],"was":[60,108,116],"evaluated":[61,94],"against":[62],"HCT-116,":[63],"MCF-7,":[64],"HepG2":[66],"cell":[67],"lines,":[68],"while":[69],"their":[70,97],"interactions":[72,138],"HDAC4,":[74],"HDAC6,":[75],"HDAC8":[77],"investigated":[79,141],"using":[80],"molecular":[81],"docking":[82,133],"induced-fit":[84,132],"docking.":[85],"Drug-likeness":[86],"in":[88,150],"silico":[89],"ADMET":[90,157],"properties":[91],"also":[93],"assess":[96],"preliminary":[98],"developability.":[99],"N-Ethylation":[100],"combined":[101],"one-,":[103],"three-,":[104],"four-carbon":[106],"linkers":[107],"associated":[109],"broader":[111],"Compound":[114],"6j":[115,192],"most":[118],"active":[119],"analog,":[120],"IC50":[122],"values":[123],"ranging":[124],"from":[125],"2":[126],"7":[128],"\u00b5M.":[129],"Docking":[130],"analyses":[134],"suggested":[135],"favorable":[136],"binding":[137,142],"within":[139],"sites,":[143],"supporting":[144],"involvement":[147],"HDACs":[149],"biological":[152],"these":[155],"compounds.":[156],"profiling":[158],"indicated":[159],"full":[160],"compliance":[161],"Lipinski\u2019s":[163],"rule":[164],"five":[166],"across":[167],"series.":[169],"Overall,":[170],"findings":[172],"identify":[173],"triazinoindole\u2013acid-hydrazide":[175],"scaffold":[176],"as":[177,194],"tunable":[180],"promising":[182],"chemotype":[184],"supported":[187],"HDAC-targeting":[188],"potential,":[189],"compound":[191],"emerging":[193],"candidate":[197],"for":[198],"further":[199],"investigation.":[200]},"counts_by_year":[],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2026-11-04T00:00:00"}