Chem. Pharm. Bull. 52(6) 659—663 (2004)

for its high cytotoxicity against several cancer cell lines due to its intercalating properties and its ability to inhibit DNA religation by topoisomerase II. A number of angular analogs have been prepared in order to obtain more active compounds. For example, one of the most promising products appeared to be intoplicine 2, synthesised firstly by Nguyen et al., which acts both as an intercalating agent and as a topoisomerase I and II inhibitor. So, considering the cytototoxic properties of angular nitrogenous heterocycles, other groups have elaborated several angular tetracyclic compounds derived from two or three nitrogenous heterocycles. Dalla Via et al. prepared indolonaphtyridines 3 carrying a dialkylaminoalkyl side chain and different substituents. Linear flow dichroism studies demonstrated these compounds were able to intercalate into DNA and in vitro cytotoxicity studies showed IC50 on HL-60 cells varying between 0.5 and 1.6 mM. Furthermore, Da Settimo et al. prepared several derivatives of purinoquinazoline 4, pyridopyrimidopurine and pyridopyrimidobenzimidazole, all of them carrying a dialkylaminoalkyl side chain. Only purinoquinazolines could bind strongly to DNA and therefore could induce DNA double-strand breaks via inhibition of DNA religation by topoisomerase II. These compounds showed IC50 on HL-60 cells varying between 0.072 and 0.47 mM. Chart 1 represents some of the structures mentionned above. Therefore, as a part of our studies related to the pharmacochemistry of angular polynitrogenous tetracycles, we initiated a program in order to examine the synthesis of new pyridopyrroloquinolines and their antitumor activities against resistant cell lines (MDR phenotype ). Our synthetic methodology resides in the use of enaminones 5 derived from quinolines and cyclopentane-1,3-dione. Key steps of the synthesis are the photocyclisation of such enaminones followed by Beckmann rearrangement to afford hydroxypyridine ring from 2-cyclopent-1-one ring, as shown in Chart 2. In this context, we have previously described the synthesis of indoloquinolines and pyridocarbazoles by photocyclisation of enaminones derived from 3 or 6-aminoquinoline and cyclohexane-1,3-dione. This present work will allow us to study the photoreactivity of new enaminones and to elaborate potentially cytotoxic compounds.