Anilinoacridines

Antitumor Activity Relationships of 9-Anilinoacridines Using Pattern Recognition. 

G. Klopman and O. T. Macina, Mol. Pharmacol., 31, 457 (1987). Computer-Automated Structure Evaluation of Anti-leukemic 9-Anilinoacridines. 

Denny, W.A., Cain, B.F., Atwell, C, Hansch, C., Panthananickal, A. and Leo, A. (1982). Potential Antitumor Agents. 36. Quantitative Relationships Between Antitumor Activity, Toxicity and Structure for the General Class of 9-Anilinoacridine Antitumor Agents. J.MetLChem., 25, 276-315. 

Henry, D.R., Jurs, PC. and Denny, W.A. (1982). Structure-Antitumor Activity Relationships of 9-Anilinoacridines Using Pattern Recognition. I.Math.Chem.,25, 899-908. 

Srivastava, A., Mishra, N. and Khan, A.A. (1995). QSAR on Some Antileukemic I -Substituted 9-Anilinoacridines with Tau Index t and Electronic Parameters. Indian J.Chem.,34B, 364-366. 

Raychaudhury C. and Klopman, G. (1990) New vertex indexes and their applications in evaluating antileukemic activity of 9-anilinoacridines and the activity of 2, 3 -dideoxy-nudeosides against HIV. Bull. Soc. Chim. Belg., 99, 255-264. 

Structuie-acdvity relationship studies with mitonafide have revealed that the compound inhibits both nuclear and mitochondrial topoisomerase of Leishmania with preferential taiget-ing of the mitochondrial enzyme over the nuclear enzyme. Anilinoacridines have recently been found to possess andparasidc activity towards Leishmania, Trypanosoma and Plasmodium species. These compounds have been shown to induce protein associated DNA lesions in L. chagasi promastigotes. Linearization of kinteoplast DNA minicirdes have also been repotted in parasites treated with anilinoacridines at similar concentrations. Members of the 9-anilinoacridine topoisomerase II inhibitors have also been shown to inhibit growth of L. major promast otes and amastigotes. 9-aminoacridines, that are reported topoisomerase II inhibitors and structurally related to the antileishmanial compound quinacrine and chlorpro-mazine, have shown anti leishmanial activity at concentrations in the range of 10-20 pM. ... 

Gamage SA, Fi itt DP, Wojcik Sj et al. Structure-activity relationships for the antileishmanial and antitrypanosomal activities of T-substituted 9-anilinoacridines. J Med Chem 1997 40 2634-42. Werbovetz KA, Lehnert EK, Macdonald TL et al. Cytotoxicity of acridine compounds for Leishmania promastigotes in vitro. Antimicrob Agents Chemother 1992 36 495-497. 

Eq. 180 was derived for the antitumor activities of 9-anilinoacridines (43) [789]. The coefficients of the n terms indicate that activities fall off more rapidly for the hydrophilic analogs as the parent compound has a log P value of about 4.8, the lipophilicity optimum can be estimated to be close to log P = 0. 

Among the N9-monosubstituted acridines from the 9-anilinoacridine series, the derivative 40, Scheme 11, possesses the bis(chloroethyl)amine substituent (a nitrogen mustard derivative) and induces monofunctional... 

Khan, M.N., Kuliya-Umar, A.F. Kinetics and mechanism of general acid-catalyzed thiolytic cleavage of 9-anilinoacridine. Bioorg. Med. Chem. 1995, 3(7), 881-890. 

---