title: Identification of antitumour activity of novel derivatives of 8-aryl-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-dione and 8-aryl-4-imino-2,3,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3(6H)-one.
abstract: The series of 8-aryl-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones (11-20) and 8-aryl-4-imino-2,3,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3(6H)-ones (21-25) were designed and their in vitro cytotoxic activities against human LS180, HeLa, T47D, A549 and RPMI 8226 carcinoma cells are presented. In the crystalline state molecule 12 exists as the predominant tautomeric 3-oxo form, whereas the second possible 3-hydroxy tautomer is not observed. Compound 19 revealed a strong affection to LS180 cancer cells at lower tested concentration (37.9 microM) and simultaneously was found to be non-toxic towards the normal cell line investigated--GMK cells. Furthermore, this compound was proved to possess the efficiency for DNA strand breakage of the examined cancer cell lines. However, imidazotriazin-3,4-dione 20 was able to cause significant viability decreases in human RPMI 8226 peripheral blood myeloma cells. Compound 22 has exhibited remarkable inhibitory effects against LS180 and A549 carcinoma cells, whereas 24 revealed the highest growth inhibition against A549 cell line. Simultaneously, at lower tested concentration these compounds were proved to be completely non-toxic for GMK cells. Moreover, cytotoxic and antibacterial properties of starting, tautomeric 1-aryl-2-hydrazonoimidazolidines (1-6 and 8-9) are presented. Six of them (1-2, 4-6 and 9) proved active as antimicrobials. All these compounds revealed MIC values in the range of 15.0-78.6 microM. Their activities were compared to those of ampicillin and chloramphenicol.
authors.affiliation: Chair and Department of Medical Chemistry, Professor Feliks Skubiszewski Medical University, 4 Staszica Street, 20-081 Lublin, Poland. krzysztof.sztanke@am.lublin.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sztanke
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Pasternak
authors.forename: Jolanta
authors.initials: J
authors.lastname: Rzymowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sztanke
authors.forename: Martyna
authors.initials: M
authors.lastname: Kandefer-Szerszeń
authors.forename: Izabela
authors.initials: I
authors.lastname: Dybała
authors.forename: Anna E
authors.initials: AE
authors.lastname: Kozioł
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002701:Chloramphenicol / Q000494:pharmacology; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007093:Imidazoles; D007202:Indicators and Reagents; D014227:Triazines; D002701:Chloramphenicol; D000667:Ampicillin