In Vitro Cytotoxicity of Imidazolyl-1,3,5-triazine Derivatives.

Abstract

We examined in vitro cytotoxic activity of imidazolyl-1,3,5-triazine derivatives using human breast cancer cell lines (MCF-7, R-27, T-47D and ZR-75-1) and murine leukemia cell line (P388). The percentage of viable cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazorium bromide (MTT) assay. Hexamethylmelamine (HMM), a 1,3,5-triazine derivative has previously been recognized as an antitumor agent effective against lung, ovarian and breast cancer, but failed to show a significant cytotoxic activity in the present study. In contrast, four imidazolyl-1,3,5-triazine derivatives, 2-(1-imidazolyl)-4,6-bis(morpholino)-1,3,5-triazine, 2-(1-imidazolyl)-4-morpholino-6-(3-thiazolidinyl)-1,3,5-triazine, 2-(4-cyano-4-phenylpiperidino)-4-(1-imidazolyl)-6-morpholino-1,3,5-triaz ine and 2-(1-imidazolyl)-4-(N-methyl-N-phenylamino)-6-morpholino-1,3,5-triazine showed cytotoxic activity for most cell lines, which was significantly greater than the activity of hydroxymethylpentamethylmelamine (HMPMM), a major metabolite of HMM.

ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system

“…ZSTK474, a promising PI3K inhibitor identified using the JFCR39 system ZSTK474 is an s-triazine derivative synthesized by Zenyaku Kogyo as an anticancer drug candidate together with more than 1500 other analogues [63] . Before its identification by the JFCR39 system, ZSTK474 showed promising antitumor efficacy, although the molecular target was unknown.…”

ZSTK474, a PI3K inhibitor, suppresses proliferation and sensitizes human pancreatic adenocarcinoma cells to gemcitabine

“…ZSTK474 is a pan-PI3K inhibitor, synthesized by Zenyaku Kogyo Co., Ltd (Tokyo, Japan) and can be given orally (14). It has shown potent anti-tumor activity against human cancer xenografts without toxic effects in critical organs (15).…”

Pharmacophore identification and bioactivity prediction for triaminotriazine derivatives by electron conformational-genetic algorithm QSAR method

“…Offspring are generated by performing a crossover (crossover probability ¼ 0.850) or a mutation (mutation probability ¼ 0.015). In a crossover, part of the (4) Distance between N1eN5 10.4968 a (5) Distance between N1eO1 0.8233 a (6) Distance between N1eN4 À43.4269 a (7) Distance between N1eH34 À1.9836 a (8) Distance between N5eO1 0.3728 a (9) Distance between N5eN4 À21.2691 a (10) Distance between N5eH34 À4.2452 a (11) Distance between O1eN4 À1.9346 a (12) Distance between O1eH34 0.7179 a (13) N4eH34 bond order 100.0000 a (14) genetic make up of one parent is mixed with part of the genetic make up of the other parent at a randomly selected crossover point. In a mutation, an individual gene (single model parameter), again selected randomly, is changed to model parameter which is not included in current chromosome for the generating offspring.…”

“…[6]. Some 1,3,5-triazines display important biological properties; for example hexamethylmelamine [7] and 2-amino-4-morpholino-s-triazine are used clinically due to their antitumor properties to treat lung, breast and ovarian cancer, respectively [8e10]. 5-Azacytidine (4-amino-1-b-D-ribofuranosyl-1,3,5-triazin-2(1H)-one), a synthetic analogue of the natural pyrimidine nucleoside cytidine, has strong antileukemic activity [11,12].…”