A series of 1-amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles that are structurally related to ellipticines by deletion of a ring have been synthesized in order to evaluate their DNA affinity, their in vitro cytotoxicity on L1210 cultured cells, and their in vivo antitumor activity. Among 24 derivatives that have been prepared and studied for the structure-activity relationship in this new class of antineoplastic agents, those that have a NH(CH2)3N(R)2 side chain (R = CH3 or C2H5) at their 1-position, a 4-methyl group, and an 8-OH substituent, either with a 5-NH or with a 5-NCH3 group, show the most potent cytotoxicities on L1210 cultured cells and in vivo antitumor properties in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed on other mouse experimental tumors from the standard NCI screening:B16 melanoma and C38 adenocarcinoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm00397a023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interrelationship between affinity for DNA, cytotoxicity and induction of DNA-breaks in cultured L1210 cells for two series of tricyclic intercalators. Simplified analogues of ellipticine derivatives.
Biochem Pharmacol
May 1989
Sanofi Recherche, Toulouse, France.
The interrelationship between affinity for DNA, cytotoxicity and induction of single-strand DNA breaks in cultured L1210 cells was studied for 21 compounds belonging to two series of tricyclic intercalators: 1-amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles (gamma CARB) and 1-amino-substituted 4-methyl-5H-pyrido[3',4':4,5]pyrrolo[2,3-c]pyridines (PPP), which are simplified analogues of Ellipticine derivatives obtained by deletion of one cycle. Adriamycin, m-AMSA (4'-(9-acridinylamino) methanesulfon-m-anisidide), PZE (10-[diethylaminopropyl amino]-6-methyl-5H-pyrido[3',4':4,5]-pyrrolo[2,3-g] isoquinoline and RTE [( 1-(3-diethylaminopropylamino)-9-methoxy ellipticine, bimaleate) are used as reference compounds. The intercalation of these compounds into DNA was strongly suggested by three experimental observations: (i) the competitive inhibition of ethidium bromide intercalation, (ii) bathochromic and hypochromic effects on absorption spectra induced by DNA, and (iii) drug-induced increase of the DNA length, measured by viscosimetry.
View Article and Find Full Text PDF1-Amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles (gamma-carbolines) as tricyclic analogues of ellipticines: a new class of antineoplastic agents.
J Med Chem
February 1988
UA 533 CNRS, Laboratoire de Synthèse Organique, Institut Curie, Orsay, France.
A series of 1-amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles that are structurally related to ellipticines by deletion of a ring have been synthesized in order to evaluate their DNA affinity, their in vitro cytotoxicity on L1210 cultured cells, and their in vivo antitumor activity. Among 24 derivatives that have been prepared and studied for the structure-activity relationship in this new class of antineoplastic agents, those that have a NH(CH2)3N(R)2 side chain (R = CH3 or C2H5) at their 1-position, a 4-methyl group, and an 8-OH substituent, either with a 5-NH or with a 5-NCH3 group, show the most potent cytotoxicities on L1210 cultured cells and in vivo antitumor properties in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed in P388 and L1210 leukemia systems.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!