Synthesis and biological screening of new 5-oximidazoline molecules possessing sulfadiazine moiety for cancer treatment

合成及生物筛选具有磺胺嘧啶部分的5-氧咪唑啉类新药用于癌症治疗

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Abstract

AIM: To synthesize a series of new 5-oximidazoline-sulfadiazine hybrids 7a-l and assess their anti-cancer (in vitro and in vivo) activities. MATERIALS AND METHODS: The antiproliferative activity was assessed against the hepatocellular carcinoma (HepG2) cell line. Moreover, the in-vitro enzymatic inhibitory activity against EGFR-TK for all the synthesized members was then assessed. In addition, cell cycle analysis, apoptosis induction, and in-vivo toxicity assessment of the most active analog were also conducted. RESULTS: The analog 7l with 3,4,5-trimethoxybenzylidene in the 5-oximidazoline ring revealed good cytotoxicity and selectivity against the HepG2 cancer cells relative to the normal cells, especially compounds 7i and 7l. Besides, in-vivo toxicity assessment revealed that compound 7l increased life-span prolongation of the EAC-bearing mice group and reduced the volume and EAC cells count in animal models. CONCLUSION: Accordingly, the afforded 5-oximidazoline-sulfadiazine hybrids represent promising lead candidates for further optimization to obtain promising anticancer agents.

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