SYNTHESIS AND ANTITUMOR-ACTIVITY OF 9-ANILINO, PHENYLHYDRAZINO, AND SULFONAMIDO ANALOGS OF 2-METHOXY-6-NITROACRIDINE OR 4-METHOXY-6-NITROACRIDINE

Synthesis of several new 9-anilino, phenylhydrazino, and sulphonamido analogs of 2- or 4-methoxy-6-nitroacridine derivatives is described. T he prepared compounds were tested for their in vitro antitumor activit y against 60 human tumor cell lines by the National Cancer Institute ( NCI) and showed a potential anticancer activity. Compounds 9-(phenylhy drazino)-2-methoxy-6-nitroacridine (8a) and 4-chlorophenylhydrazino)-4 -methoxy-6-nitroacridine (9b) exhibited a broad spectrum antitumor act ivity with full panel(MG-MID) median growth inhibition (GI(50)), of 16 .1 and 10.9 mu M and total growth inhibition (TGI) of 66.7 and 37.9 mu M, respectively. Meanwhile, compounds 15a and 15b showed moderate sel ectivity toward leukemia cell lines. As a trial to explore the mode of action of their antitumor activity, the 6-nitroacridine analogs were evaluated for their inhibitory effect on major cell cycle control prot eins cdc2 kinase and cdc25 phosphatase as possible molecular targets t hat may account for antimitotic potency. None of the tested compounds proved to exert their activity via this antimitotic mode of action.