Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity.
A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the 'rule-of-five' claims by Lipinski and calculated logP(calc) values were experimentally confirmed (logP(exp)). For the most active compounds, in vitro serum albumin binding was investigated and structure-activity relationships were established.
Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, 06120 Halle, Germany. fabian.krauth@pharmazie.uni-halle.de
Fabian
F
Krauth
Hans-Martin
HM
Dahse
Hans-Hermann
HH
Rüttinger
Petra
P
Frohberg
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D012709:Serum Albumin / Q000737:chemistry; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity
C549970:2,3,4,5-tetrahydro-4-(2-chlorophenyl)-2-phenyl-6-(pyrrolidin-1-yl)-1,2,4-triazin-5-one; D000970:Antineoplastic Agents; D011759:Pyrrolidines; D012709:Serum Albumin; D014227:Triazines; C093444:1,2,4-triazine