Evaluation of the mutagenic/clastogenic potential of 3,6-di-substituted acridines targeted for anticancer chemotherapy.

The mutagenicity and clastogenicity of a series of 18 3,6-di-substituted acridines were evaluated by the Ames test on Salmonella typhimurium TA 97a and by the micronucleus assay on Chinese Hamster Ovary cells (CHO cells), as compared to their cytotoxicity against CHO cells. Experimental results overall demonstrated that simple symmetric molecules were more mutagenic than asymmetric structures. The mutagenic properties of acridines on strain TA97a mainly depended on molecular geometry and length, and on the nature of the substituted groups.

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 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[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.

Differentiation of heterocyclic regioisomers: a combined tandem mass spectrometry and computational study of N-acridin-4-ylbenzylamide and N-acridin-2-yl-benzylamide.

Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) has been used to differentiate two positional isomers of acridine derivatives, N-acridin-4-ylbenzylamide and N-acridin-2-ylbenzylamide. The study revealed that the isomeric ion structures produced by these heterocycles could be distinguished upon collision-induced dissociations (CID). In particular, the loss of a water molecule was shown to be a regiospecific reaction of the protonated N-acridin-4-ylbenzylamide, in which the location of the benzylamide substituent with respect to the acridinic nitrogen greatly assists proton migration by allowing the creation of intramolecular hydrogen bonds.