Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine

The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay.Compounds 2ftert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2dN-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.

A series of 18 3,6-di-substituted acridines were synthesized and assessed for their photo-enhanced cytotoxic and clastogenic activities. Compounds 2ftert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate, 2d (N-[6-(pivalamino)acridin-3-yl]pivalamide) and 4b (N-(3-(furan-2-carboxamido)acridin-6-yl)furan-2-carboxamide) displayed a specific cytotoxicity on tumour cells. The presence of a 1,1-dimethylethyl substituent was responsible for a nonclastogenic cytotoxicity, whereas nonramified aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Most of the acridine compounds could be photo-activated by UVA–visible rays.Figure optionsDownload as PowerPoint slide