Synthesis and structure-activity relationships of andrographolide analogues as novel cytotoxic agents.
Andrographolide 1, the cytotoxic agent of the plant Andrographis paniculata was subjected to semi-synthetic studies leading to the preparation of a number of potent and novel analogues. Of the analogues synthesized, while 8,17-epoxy andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6 exhibited considerable improvement in activity. Lower activity was observed when the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and structure-activity relationships are discussed.
Discovery Chemistry, Dr. Reddy's Laboratories Ltd, Discovery Research, Bollaram Road, Miyapur, Hyderabad 500 049, India. nandurisrinivas@drreddys.com
Srinivas
S
Nanduri
Vijay Kumar
VK
Nyavanandi
Siva Sanjeeva Rao
SS
Thunuguntla
Sridevi
S
Kasu
Mahesh Kumar
MK
Pallerla
P Sai
PS
Ram
Sriram
S
Rajagopal
R Ajaya
RA
Kumar
Rajagopalan
R
Ramanujam
J Moses
JM
Babu
Krishnamurthi
K
Vyas
A Sivalakshmi
AS
Devi
G Om
GO
Reddy
Venkateswarlu
V
Akella
D035685:Andrographis; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide