Positive antitumor activities, reveal

In 2003, the group of Banik has assayed some 2-azetidinones against nine human cancer cell lines as a measure of cytotoxicity [86]. Structure-activity studies have revealed that A-chrysenyl- and A-phenantrenyl-3-acetoxy-4-aryl-2-azetidinones (Fig. 46), respectively, have potent anticancer activity. The comparable /V-anthra-cenyl, A-pyrenyl, and A -naphthalenyl derivatives became inactive. It is evident that the minimal structural requirement of the aromatic moiety for cytotoxicity is at least three aromatic rings in an angular configuration. The presence of the acetoxy group at the C-3 position of the (3-lactams has proved to be obligatory for their antitumor activity [86]. 

An extensive study by Roques and co-workers (102) of the cytotoxicity, antitumor activity, and DNA binding affinities of a series of 7//-pyridocarbazole monomers and dimers is presented in Tables VIII and IX. These data reveal the importance of methyl substitution at positions C-6 or C-7 in the N-2 monomers... 

HI El-Subbagh et al. [76] S3mthesized a sequence of 2,4-disubstituted thiazole compounds containing N-n-butyl or N-cyclohexyl thioureido synthon at position-2 and N-substituted thiosemicarbazone moiety 25 at position-4 and verified for antitumor activity. All of the established derivatives revealed antineoplastic activity at concentrations less than 10 pM. 

Numerous titanocene derivatives ( 5115)271X2 were tested which had been modified at the position of the acido ligands X. Investigating the antitumor activity of titanocene dihalides and bis(pseudohalides) VII-XI revealed compounds which were equally potent as I, the optimum cure rate amounting to 100%. In the case of VIII with X = Br, the therapeutic range was enlarged leading to an increase of the therapeutic index (T.I.) to 4.5 (Fig. 9), compared with 3.3 after application of I. 

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