Design and synthesis of novel quinazoline nitrogen mustard derivatives as potential therapeutic agents for cancer

Abstract

Thirteen novel quinazoline nitrogen mustard derivatives were designed, synthesized and evaluated for their anticancer activities in vitro and in vivo. Cytotoxicity assays were carried out in five cancer cell lines (HepG2, SH-SY5Y, DU145, MCF-7 and A549) and one normal human cell line (GES-1), in which compound 22b showed very low IC50 to HepG2 (the IC50 value is 3.06 μM), which was lower than Sorafenib. Compound 22b could inhibit cell cycle at S and G2/M phase and induce cell apoptosis. In the HepG2 xenograft model, 22b exhibited significant cancer growth inhibition with low host toxicity in vivo.

Keywords: (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 4-dimethylaminopyridine; A549; Anticancer; Apoptosis; Cell cycle; DMAP; DU145; FBS; HCC; HepG2; MCF-7; MTT; Nitrogen mustard; PBS; PI; Quinazoline; RNase A; SH-SY5Y; Xenograft model; fetal bovine serum; hepatic carcinoma; human alveolar adenocarcinoma cell line; human breast cancer cell line; human liver carcinoma cell line; human neuroblastoma cell line; human prostate cancer cell lines; phosphate buffer solution; propidium iodide; ribonuclease A.