Design and synthesis of C-ring lactone- and lactam-based podophyllotoxin analogues as anticancer agents.
A series of novel podophyllotoxin (PDT) analogues was synthesized in which the lactone moiety was shifted to C ring. Some of the derivatives were also synthesized with modified A ring. Analogues 23 and 25 exhibited potent in vitro cytotoxicity against colon cancer (CaCO(2)) cell line. p-Demethylated E-ring analogues exhibited better potency than the corresponding methylated analogues. These analogues showed toxicity comparable to PDT against human erythrocytes albeit at much higher concentrations (100 microg/ml) than their cytotoxicity values.
Singh
Pragya
P
Central Institute of Medicinal and Aromatic Plants (CIMAP-CSIR), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow-226 015, India.
Faridi
Uzma
U
Srivastava
Suchita
S
Kumar
Jonnala Kotesh
JK
Darokar
Mahender Pandurang
MP
Luqman
Suaib
S
Shanker
Karuna
K
Chanotiya
Chandan Singh
CS
Gupta
Atul
A
Gupta
Madan Mohan
MM
Negi
Arvind Singh
AS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007769:Lactams / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007769:Lactams; D007783:Lactones; D011034:Podophyllotoxin