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.
In the context of the design and synthesis of DNA ligands, some new hetarene annelated carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds was examined by the NCI antitumor screening. Furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA-binding properties and inhibition of DNA related functional enzymes of this new series of molecules.
Lemster
Thomas
T
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Johannes Gutenberg-University, Mainz, Rheinland-Pfalz, Germany. lemster@uni-mainz.de
Pindur
Ulf
U
Lenglet
Gaelle
G
Depauw
Sabine
S
Dassi
Christelle
C
David-Cordonnier
Marie-Hélène
MH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003500:Cyclization; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D005453:Fluorescence; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D009691:Nucleic Acid Denaturation; D055668:Photochemical Processes; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D044366:Transition Temperature
D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004247:DNA