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.
Nanduri
Srinivas
S
Discovery Chemistry, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram Road, Miyapur, Hyderabad 500 050, India. nandurisrinivas@drreddys.com
Thunuguntla
Siva Sanjeeva Rao
SS
Nyavanandi
Vijay Kumar
VK
Kasu
Sridevi
S
Kumar
P Mahesh
PM
Ram
P Sai
PS
Rajagopal
Sriram
S
Kumar
R Ajaya
RA
Deevi
Dhanvanthri S
DS
Rajagopalan
R
R
Venkateswarlu
A
A
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