Synthesis of pyrrolo[3,2-h]quinolinones with good photochemotherapeutic activity and no DNA damage

Pyrrolo[3,2‐h]quinazolines as Photochemotherapeutic Agents

“…[10] Tetrahydroisoindole-4-ones 7 a-g, suitable substrates for our purpose, were prepared by a method previously reported by us. [8] They are considered ideal building blocks in organic synthesis, as they can be easily functionalized with enamine or formyl functionalities at position a to the carbonyl group. The annular carbonyl group and the exocyclic carbon bound at position 6 are, in fact, two electrophilic centers readily available to react with dinucleophiles such as urea, guanidines, hydroxyamines, and cyanomethylenic compounds to achieve further annulation.…”

“…We also investigated a different condensation of the pyrrole ring in the tricyclic system, leading to the pyrrolo[3,2-h]quinolinone 5. [8] This compound class shows remarkable phototoxicity as photochemotherapeutic agents (0.5-7.2 mm), and studies designed to elucidate the mechanism of action revealed that they photo-induce cell death by apoptosis. However, the most important feature of these compounds is that they exert their remarkable activity without in vitro DNA damage, which is the main cause of the long-term side effects (mutagenesis and increased risk of cutaneous tumors) of PUVA therapy.…”

Induction of erythroid differentiation and increased globin mRNA production with furocoumarins and their photoproducts

“…Erythroid differentiation was determined by counting blue benzidine-positive cells after suspending the cells in a solution containing 0.2% benzidine in 10% H 2 O 2 and 0.5 M glacial acetic acid [7]. Cell phototoxicity was assessed by the MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)] test 5 days after irradiation [20]. The irreversibility of erythroid differentiation was also assessed: 6 days after irradiation, 10,000 cells were plated in a new plate with fresh medium and after further 4 days, they were counted after benzidine-staining as elsewhere described [21].…”

“…Samples were analyzed on a BD FACS Calibur flow cytometer collecting 10,000 events. Results of cell-cycle analysis were examined using WinMDI 2.9 (Windows Multiple Document Interface for Flow Cytometry) [20].…”

Synthesis of substituted isoindolo[2,1-a]quinoxalin-6-yl–amino and 6-imino-5-yl thiourea derivatives

“…Quinoxalinylethylpyridylthioureas (QXPTs) of type 1 and 2 ( Figure 2) represent another class of NNRTIs; many compounds showed a potent activity against both HIV-1 wild-type RT and various HIV-1 mutants HIV-1 RT. 16 Considering the good experience reached in the course of our researches on polycyclic nitrogen systems, bearing pyrrole, [17][18][19][20][21][22][23][24] indole, [25][26][27][28][29][30][31][32][33][34][35] isoindole 36-38 and indazole …”