title: Structure-activity relationships for 4-anilinoquinoline derivatives as inhibitors of the DNA methyltransferase enzyme DNMT1.
abstract: A series of 4-anilinoquinoline derivatives related to the known inhibitor SGI-1027, containing side chains of varying pK(a), were prepared by acid-catalysed coupling of the pre-formed side chains with 4-chloroquinolines. The compounds were evaluated for their ability to reduce the level of DNMT1 protein in HCT116 human colon carcinoma cells by Western blotting. With a very strongly basic N-methylpyridinium side chain, only NHCO-linked compounds were effective, whereas less strongly basic ((diaminomethylene)hydrazono)ethyl or 3-methylpyrimidine-2,4-diamine side chains allowed both NHCO- and CONH-linked compounds to show activity. In contrast, the pK(a) of the quinoline unit had little apparent influence on activity.
authors: Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Auckland 1142, New Zealand.
authors: Swarna A
authors: SA
authors: Gamage
authors: Darby G
authors: DG
authors: Brooke
authors: Sanjeev
authors: S
authors: Redkar
authors: Jharna
authors: J
authors: Datta
authors: Samson T
authors: ST
authors: Jacob
authors: William A
authors: WA
authors: Denny
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011804:Quinolines; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human