Synthesis and Biological Evaluation of 11-Substituted 6-Aminobenzo[c]phenanthridine Derivatives, a New Class of Antitumor Agents

Abstract

The synthesis of 11-substituted 6-amino-11,12-dihydrobenzo[c]phenanthridines and 11-substituted 6-aminobenzo[c]phenanthridines through an efficient method is described. The antiproliferative activity of selected compounds against a wide panel of tumor cell lines was tested in the in vitro anticancer screening and the in vivo hollow fiber assay of the National Cancer Institute. Several compounds turned out to exhibit considerable cytotoxicity for tumor cells. For the study of structure-activity relationships different substituents were introduced in the 11-position. Compounds with methoxyphenyl substituents tended to show the highest potency. Several compounds exhibited noteworthy antitumor activity with GI(50) values across all cell lines <1 microM. 6-Amino-11-(3,4,5-trimethoxyphenyl)benzo[c]phenanthridine perchlorate was the most potent agent in the NCI's in vivo hollow fiber assay. Most of the tested compounds showed a remarkable selectivity for leukemia, breast cancer, and prostate cancer.

Novel bis-phenanthridine derivatives with easily tunable linkers, study of their interactions with DNA and screening of antiproliferative activity

“…[1][2][3] In addition, it was shown that the chemical modulation of the ethidium substituents is a profitable option to tune the nucleic acid recognition properties of phenanthridine dyes. [4] Very recent reports about numerous applications point toward versatility of the phenanthridine core, [5][6][7][8][9] including even intriguing biological activity. [10] A huge number of bis-phenanthridine derivatives were prepared with the aim of not only enhanced affinity due to the bis-intercalation into DNA/RNA but also with the idea of introducing selectivity.…”

Synthesis and PC3 androgen-independent prostate cells antiproliferative effect of fagaronine derivatives

“…To overcome this problem, Clement et al recently described the synthesis and the antitumoral activity of 6-aminobenzo[c ]phenanthridine derivatives, also bearing a phenyl group on C-11. These molecules were shown to be very potent agents against various tumour cell lines [19]. Compared to our BZP series, the iminium function, characterized by its positively charged nitrogen, has been replaced by an amidine group, potentially bearing a positive charge.…”

Progresses in Synthesis of Benzophenanthridine Alkaloids and Their Derivatives

“…苯甲醛中取代基 R 为供电子烷氧基或卤素原子时 对整个反应的得率没有影响 [53] . 但是以甲醛为原料时 目标产物 6-氨基-11,12-二氢苯并啡啶(118)的得率降低 至 11%, 影响 118 得率的原因仍然有待研究.…”