Biological investigation and structure-activity relationship studies on azadirone from Azadirachta indica A. Juss.
Azadirone 1, a limonoidal constituent of Azadirachta indica is found to possess potent cytotoxic activity against a panel of human cancer cell lines in our in vitro studies. In vitro screening of a number of semi-synthetic analogues of 1 revealed that the alpha,beta-unsaturated enone moiety or its equivalent conjugated system in A-ring, C-7 acetyloxy/chloroacetyloxy or keto group in B-ring and the furan moiety are responsible for the activity of 1 and its analogues. Compound 1 and two of the semi-synthetic analogues 10 and 13 were found to possess good in vivo antitumor activity in modified hollow fiber animal models.
Discovery Chemistry, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram Road, Miyapur, Hyderabad 500 050, India. nandurisrinivas@drreddys.com
Srinivas
S
Nanduri
Siva Sanjeeva Rao
SS
Thunuguntla
Vijay Kumar
VK
Nyavanandi
Sridevi
S
Kasu
P Mahesh
PM
Kumar
P Sai
PS
Ram
Sriram
S
Rajagopal
R Ajaya
RA
Kumar
Dhanvanthri S
DS
Deevi
R
R
Rajagopalan
A
A
Venkateswarlu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D031601:Azadirachta / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D036701:Limonins / Q000138:chemical synthesis / Q000302:isolation & purification / Q000633:toxicity*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D036701:Limonins; C487479:azadirone