Antitumor activity indolo carbazole

Several natural and synthetic inhibitors of the family of enzymes known as protein kinases have been discovered, and many of these compounds have antitumor activity. The natural indolo-carbazole alkaloids are discussed separately. 

The tjipanazoles (18, 19a-d, 20a-b) a group of A-glycosides of indolo-[2,3-a]carbazole, have been isolated from the moderately antifungal extract of the blue-green alga Tolypothrix tjipanasensis. These alkaloids do not exhibit antitumor or protein kinase C (PKC) inhibitory activity, which is in contrast with the... 

The majority of indolocarbazole alkaloids, isolated so far from nature, are derivatives of the indolo[2,3-fl]pyrrolo[3,4-c]carbazole ring system 292. They have been isolated from soil organisms, slime molds, and marine sources (3,7,8,252-255), and have shown a broad range of potent biological activities, such as antifungal, antimicrobial, antitumor, and antihypertensive activity (3,7,256-260,267-270). Their activity as potent inhibitors of protein kinase C (PKC) has received special attention, and was the focus of several investigations (8,257,258,271-280). The history of these natural products dates back about 30 years (Scheme 2.73). 

This chemistry has provided one of the most direct routes to the indolo[2,3-a]carbazole alkaloid ring system (Scheme 11), a common functionality of several biologically active molecules such as the potent antitumor agent rebeccamycin and arcyriaflavin A. The indolo[2,3-fl]carbazole derivative has been obtained in satisfactory yield through the reaction of l,4-di((9-trifluoroacetamidophenyl)-l,3-butadiyne with 3,4-dibromomaleimide in the presence of tetrakis(triphenylphosphine)palladium(0) and potassium carbonate. The proposed mechanism of this polyannulation process, which generates four new bonds in a single step, is outlined in Scheme 12. 

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