Synthesis and identification of novel indolo[2,3-a]pyrimido[5,4-c]carbazoles as a new class of anti-cancer agents.
A range of 5,6-bisindole and 5-indole-6-(7-azaindole)pyrimidinones were synthesised via a β-keto ester intermediate and a screen of cyclisation conditions undertaken. The optimised route to this new class of indolocarbazoles and azaindolocarbazoles involved photocyclisation, with typical yields of 50-60%. These derivatives were screened for anti-cancer activity via topo II inhibition and the NCI-60 cell line assay, with the screening indicating a lack of topo II inhibition, but significant in vitro growth inhibition within this new chemical class, in the low micromolar range against renal cancer, melanoma and colon cancer cell lines.
Department of Chemistry, Analytical and Biological Research Facility, University College Cork, Western Road, Cork, Ireland.
Larry T
LT
Pierce
Michael M
MM
Cahill
Hannah J
HJ
Winfield
Florence O
FO
McCarthy
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II