199806-33-2

Upstream product

• 122745-42-0 1-Chloromethyl-2,3-dihydro-1H-benzo[e]indol-5-ol; hydrochloride 
• 199805-82-8 5-[(5-acetamido-1H-indol-2-ylcarbonyl)amino]-1H-indole-2-carboxylic acid 
• 71086-99-2 ethyl 5-amino-1H-indole-2-carboxylate 
• 199805-81-7 5-[(5-acetylamino-1H-indole-2-carbonyl)-amino]-1H-indole-2-carboxylic acid ethyl ester 
• 199805-80-6 5-(acetylamino)indole-2-carboxylic acid 
• 110887-42-8 ethyl 5-acetamido-1H-indole-2-carboxylate 
• 122745-46-4 1,2,9,9a-tetrahydrocyclopropa[e]benz[e]indol-4-one 
• 16732-57-3 5-nitro-indole-2-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

CC-1065 analogues bearing different DNA-binding subunits: Synthesis, antitumor activity, and preliminary toxicity study

CC-1065 analogues bearing different DNA-binding subunits were synthesized. A terminal C5-NO2 and -F moiety at the DNA-binding subunit increased the drug's potency and antitumor efficacy. A C5-OCH3 reduced the potency and antitumor efficacy. Compound (±)-7, bearing a trans double bond, had increased antitumor efficacy. A preliminary toxicity study indicated that terminal C5-OCH3 and -acetamido moieties at the DNA-binding subunit caused delayed death in mice.

Synthesis and preliminary biological evaluations of CC-1065 analogues: Effects of different linkers and terminal amides on biological activity

CC-1065 analogues possessing a biologically active CBI functional group and amide-substituted indole and benzofuran were synthesized. The IC50 values of compounds 26, bearing two indoles, and 25, bearing only one indole, are 0.4 and 3 nM, respectively, against U937 leukemia cells in vitro. The IC50 values of compounds 28, bearing a butyramino group, and 27, bearing an acetamino group, are 0.008 and 0.4 nM, respectively, against U937 leukemia cells in vitro. Compound 29, bearing a double-bond linker, is about 4-fold more potent than 25, bearing no double-bond linker. Compound 26 is highly potent against all cell lines tested in the NCI in vitro screening with IC50 values in the 0.1-5 nM range for most cell lines. Compounds 26 and 30 are highly active against L1210 leukemia in mice. Compound 26 is also active against B16BL6 melanoma in mice. Most importantly, 26 and 30 are not myelosuppressive at therapeutically effective doses. The mechanism of tumor cell death is through induction of apoptosis, and is accompanied by DNA fragmentation.