In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c]phenanthridines in the absence of a benzene A-ring. All novel compounds were prepared from 6-bromo-2-hydroxy-3-methoxybenzaldehyde in several synthetic steps through reduction of Schiff bases and accomplished by radical cyclization. Twelve derivatives showed high antibacterial activity against Bacillus subtilis, Micrococcus luteus and/or Mycobacterium vaccae at single digit micromolar concentrations. Some compounds also displayed cytotoxicity against the K-562 and MCF-7 cancer cell lines at as low as single digit micromolar concentrations and were more potent than chelerythrine and sanguinarine. The active compounds caused cell-cycle arrest in cancer cells, increased levels of p53 protein and caused apoptosis-specific fragmentation of PARP-1. Biological activity was connected especially with the presence of the N-methyl quaternary nitrogen and 7-benzyloxy substitution (compounds 7i, 7j, 7k, and 7l) of phenanthridine.

A series of arylhydrazones 1a-1i was prepared by coupling of arene diazonium salts with ethyl N-(benzo[b]furan-2-yl)carbamate. The hydrazones 1 were thermally cyclized to the corresponding 2-aryl[1]benzofuro[2,3-e][1,2,4]triazin-3(2H)-ones 2a-2i, derivatives of a new fused ring system. Compounds 2 were transformed by hydrolytic splitting to the corresponding 1-aryl-5-(2-hydroxyphenyl)-6-azauracils 3a-3i.

A simple general synthesis of 1-aryl-6-azaisocytosine-5-carbonitriles 4 is described. This method is based on coupling diazonium salts with cyanoacetylcyanamide 2 and then cyclization of the formed 2-arylhydrazono-2-cyanoacetylcyanamides 3. The 6-azaisocytosines 4 were studied with respect to tautomeric equilibrium and the transformation of functional groups, and used in the synthesis of the condensed heterocyclic compounds: Purine isosteric imidazo[2,1-c]-[1,2,4]triazine 8 and the 1,2,4-triazino[2,3-a]quinazolines 9–12.

A new N⁷ direct regioselective method allowing the introduction of tert-alkyl groups into appropriate 6-substituted purine derivatives is developed. This method is based on a reaction of N-trimethylsilylated purines with a tert-alkyl halide using SnCl₄ as a catalyst. In this work, we study the structure and optimal reaction conditions leading to the N⁷ isomer and in some cases also to the N⁹ isomer. The main goal is devoted to preparing 7-(tert-butyl)-6-chloropurine as a suitable compound for other purine transformations. The stability of the tert-butyl group at the N⁷ position is tested for classic model reactions, leading to the preparation of new 6,7-disubstituted purine derivatives, which is also interesting from the point of view of possible biological activity.