Novel olivacine and ellipticine derivatives: S-16020-2 and related compounds as potential antitumor agents

Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and antitumor cell cytotoxicity

“…Thus, in continuation of our synthetic efforts in carbazole and carbazole alkaloid chemistry [12,13], we studied new short and flexible routes to some hetarene-[a]-annelated carbazoles of type 10. Moreover, derived from some literature reports [3,7,14] and from our own results in the netropsin series [15][16][17][18][19], the selective introduction of a dimethylaminoalkylcarboxamide group at the coplanaric chromophoric system should be of significant importance for a selective DNA binding and antitumor activity. For example DACA (N-[2-(dimethylamino)-ethyl]-acridine-4-carboxamide) 5 is a dual topoisomerase I/II inhibitor and DNA intercalator with potent cytotoxicity against leukaemia cell lines.…”

“…Since the discovery of the natural products ellipticine 1 and its regioisomeric olivacine 2 annelated indole and carbazole derivatives with pyrido [4,3-b]carbazole framework constitute an interesting class of antitumor active drugs [1][2][3][4]. Whereas ellipticine 1 as well as 9-methoxyellipticine 3 shows activity against a variety of human tumor cell lines, especially against leukaemia, the quarternary pyridinium salt ellipticinium acetate (Celliptium Ò ) 4 was deployed against metastatic breast cancer [3,5].…”

“…Whereas ellipticine 1 as well as 9-methoxyellipticine 3 shows activity against a variety of human tumor cell lines, especially against leukaemia, the quarternary pyridinium salt ellipticinium acetate (Celliptium Ò ) 4 was deployed against metastatic breast cancer [3,5]. The mechanism of action in vivo of ellipticine and variants via DNA-intercalation process, bioactivation due to oxidation at C-9 and indirect topoisomerase II-inhibition is well described [4,6].…”

“…The mechanism of action in vivo of ellipticine and variants via DNA-intercalation process, bioactivation due to oxidation at C-9 and indirect topoisomerase II-inhibition is well described [4,6]. In this context many derivatives based on the linear annelated carbazole ellipticine and olivacine were synthesized for the development of new DNAintercalating anticancer drugs [2,3,7]. However, only a few studies were carried out with compounds bearing an angled pyridocarbazole anellation [6,11].…”

Synthesis and Cytotoxic Activity of Benzophenanthrolinone Analogues of Acronycine.

“…8,9) The replacement of the dimethylpyran D ring of acronycine by a pyridine unit, present in numerous tetracyclic antitumor drugs including the linear ellipticines [10][11][12] and olivacines, [13][14][15] and their angular 7H-and 11H-pyridocarbazoles counterparts, [16][17][18][19] appeared to us an attractive way to look for new anticancer candidates. In addition, this approach was consistent with the antitumor activities of several recently described benzophenanthrolinones related to amsacrine.…”