Antineoplastic Activity of Water-Soluble Form of Novel Kinase Inhibitor 1-(4-Chlorobenzyl)-3-Chloro-4-(3-Trifluoromethylphenylamino)-1H-Pyrrole-2,5-Dione Immobilized on Polymeric Poly (PEGMA-co-DMM) Carrier

The maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1H-pyrrole-2,5-dione (MI-1) was synthesized as inhibitor of several protein kinases, however, its application is hindered by poor water solubility. In this study, the mechanisms antineoplastic action MI-1 and MI-1/M5 complex with M5 carrier (poly (PEGMA-co-DMM)) towards human colon carcinoma HCT116 cells were investigated using MTT clonogenic assays, DNA intercalation methyl green replacement, alkaline comet assay, Western-blot analysis. compound possessed high toxicity (HCT116), cervical (HeLa) melanoma (SK-MEL-28) GI50 value in a range 0.75–7.22 µg/mL, demonstrated selectivity index (SI ˃ 6.9). p53 status cancer did not affect sensitivity these to treatment complex. polymer low studied cells. MI-1, MI-1/M5, only slightly inhibited growth pseudo-normal HaCaT Balb/c 3T3 cell lines (GI50 50 μg/mL). induced mitochondria-dependent pathway apoptosis, damage DNA, morphological changes cells, affected G2/M transition checkpoint. intercalated into molecule, while such capability much lower. Thus, poly (PEGMA-co-DMM) might be promising for delivery derivative, novel kinase inhibitor, through improving solubility aqueous media enhancing antiproliferative tumor Studies are progress on Nemeth-Kellner lymphoma (NK/Ly)-bearing mice