title: In vitro and in vivo anticancer activity of 2-deacetoxytaxinine J and synthesis of novel taxoids and their in vitro anticancer activity.
abstract: 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).
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattrar Manzil, Lucknow 226 001, Uttar Pradesh, India.
authors.forename: K Papi
authors.initials: KP
authors.lastname: Reddy
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Bid
authors.forename: V Lakshma
authors.initials: VL
authors.lastname: Nayak
authors.forename: Preeti
authors.initials: P
authors.lastname: Chaudhary
authors.forename: J P
authors.initials: JP
authors.lastname: Chaturvedi
authors.forename: K R
authors.initials: KR
authors.lastname: Arya
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
authors.forename: T
authors.initials: T
authors.lastname: Narender
mesh_terms: 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*
chemical_list: C519723:2-deacetoxytaxinine J; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids