Optimization of naphthalimide-imidazoacridone with potent antitumor activity leading to clinical candidate (HKH40A, RTA 502).
Unsymmetrical bifunctional antitumor agent WMC79 was further optimized to generate compound 7b that not only inhibited the growth of many tumor cell lines, but caused rapid apoptosis. Unlike the parent compound, 7b is toxic to both p53 positive and negative cancer cells. It has potent in vivo activity against xenografts of human colon and pancreatic tumors in athymic mice.
Hariprakasha
Humcha K
HK
Molecular Aspects of Drug Design Section, Structural Biophysics Laboratory, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA.
Kosakowska-Cholody
Teresa
T
Meyer
Colin
C
Cholody
Wieslaw M
WM
Stinson
Sherman F
SF
Tarasova
Nadya I
NI
Michejda
Christopher J
CJ
D054831:Acridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D054831:Acridones; D000970:Antineoplastic Agents; D053644:Naphthalimides; C525457:RTA 502; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53