Abstract
A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1–14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR) study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed.
Highlights
Marine invertebrates are rich in -carboline alkaloids [1,2,3]
To improve our knowledge of the main structural requirements needed for high antitumor activity, we synthesized two new series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- -carboline and carbazolyl-3,4-dihydro- -carboline derivatives based on the analog design of manzamine A
With the aim of studying the structure and activity relationship (SAR), we focused on the lengh of the N-alkyl side chain on the carbazole ring
Summary
Marine invertebrates are rich in -carboline alkaloids [1,2,3]. These natural -carboline metabolites have been found to possess interesting antitumor and antiviral activities [4,5,6]. In order to investigate the structure and activity relationship (SAR) and bioactive center of manzamine A, the synthesis of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro- -carboline derivatives were initiated [17]. A facile synthetic method by the application of N-alkylation, Duff reaction [18], Pictet-Spengler reaction [19,20] and DDQ oxidation [21] succeeded in the production of compounds 1–18. In this communication, we wish to report the preparation, structural elucidation and bioactivities of.
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