In vitro and in vivo anticancer activity of 2-deacetoxytaxinine J and synthesis of novel taxoids and their in vitro anticancer activity.
The taxane diterpneoid 2-deacetoxytaxinine J (2-DAT-J) 1 has been isolated from the bark of Himalayan yew, Taxus baccata L. spp. wallichiana in a reasonably good yield (0.1%) and its anticancer activity against breast cancer cell lines (MCF-7 and MDA-MB-231) and normal human kidney epithelial cell line (HEK-293) has been studied. 2-DAT-J (1) showed significant in vitro activity against breast cancer cell line at a concentration of 20 microM and 10 microM in MCF-7 and MDA-MB-231 respectively. Few novel taxoids were derived (7, 8 and 10-13) from the naturally occurring 2-DAT-J (1) and screened for their anticancer activity. The structure-activity relationship studies indicated that the cinnamoyl group on C-5 and acetyl group on C-10 are essential for the anticancer activity. 2-DAT-J (1) was also tested for its in vivo activity on DMBA-induced mammary tumors in virgin female Sprague Dawley rats at a dose of 10mg/kg body weight orally for 30 days and showed significant regression in mammary tumors as compared to vehicle treated group (p<0.05).
Reddy
K Papi
KP
Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattrar Manzil, Lucknow 226 001, Uttar Pradesh, India.
Bid
Hemant K
HK
Nayak
V Lakshma
VL
Chaudhary
Preeti
P
Chaturvedi
J P
JP
Arya
K R
KR
Konwar
Rituraj
R
Narender
T
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000166:cytology; D024301:Plant Bark / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D020946:Taxus / Q000737:chemistry*
C519723:2-deacetoxytaxinine J; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids