A series of pyrimidoacridine derivatives with two basic side chains, 7a-e, was synthesized, as potential antitumor drugs, starting from 2-[2-(dimethylamino)ethyl]-6-chloropyrimido[5,6,1-de]acridine-1,3, 7- trione (6) and a suitable (alkylamino)alkylamine. The products 6 and 7a-e showed significant cytotoxic activity in vitro against L1210 leukemia. Compounds 7a,d were 2 orders of magnitude more cytotoxic than ametantrone. All compounds were also examined for their activity on LoVo and resistant LoVo/Dx cell lines. Unlike ametantrone, the compounds have shown to be able to overcome the multidrug resistance. Compounds 7a,d, the two most active in vitro, were tested in vivo against murine P388 leukemia showing good activity.

No abstract

Synthesis of 9,10-Anthraquinone Monoalkylaminoalkylhydrazones as Potential Antitumor Drugs.-The clinical use of anthracyclines as antitumor agents has been limited because of their cumulative, dose-dependent cardiotoxicity. The redox cycling activity of the quinone moiety of this class is responsible for the production of reactive oxygen species, such as hydroxy radicals, capable of initiation lipid peroxidation. Structural modifications of the quinone moiety prevent such negative effects. Compounds (IIIb) and (IIIc) are devoid of cytotoxic activty, whereas compounds (IIIa) and (IIId) possess only marginal activity. -(ANTONINI, I.; POLUCCI, P.; COLA, D.; PALMIERI, G.; MARTELLI, S.; BONTEMPS-GRACZ, M.; Farmaco, Ed.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.