ABSTRACT
A one-pot chemical process using BF(3).Et(2)O for the synthesis of a new class of 1(15-->11) abeotaxanes from normal taxanes has been developed. The chemical structures of rearranged 1(15-->11) abeotaxane were established by extensive 2D NMR spectroscopic data.
Subject(s)
Taxoids , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Paclitaxel/chemistry , Paclitaxel/isolation & purification , Taxoids/chemical synthesis , Taxoids/chemistry , Taxoids/classificationABSTRACT
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).
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Taxoids/chemistry , Taxoids/therapeutic use , Taxus/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/toxicity , Breast Neoplasms/chemically induced , Cell Line , Cell Line, Tumor , Epithelial Cells/cytology , Epithelial Cells/drug effects , Female , Humans , Inhibitory Concentration 50 , Kidney/cytology , Plant Bark/chemistry , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Taxoids/isolation & purification , Taxoids/toxicityABSTRACT
Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (+/-8.07)% against established VL in hamsters at a dose of 100mg/kgb.wt.
Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Chemistry, Pharmaceutical/methods , Leishmania donovani/metabolism , Quinazolines/chemistry , Quinazolines/pharmacology , Administration, Oral , Animals , Biological Assay , Cricetinae , Crystallography, X-Ray/methods , Drug Design , Humans , Macrophages/metabolism , Macrophages/parasitology , Magnetic Resonance Spectroscopy , Mice , Peganum/metabolism , Plant Extracts/metabolismABSTRACT
An efficient method is developed for the synthesis of the modified triprenylated chalcone, munchiwarin (1), isolated from the roots of Crotalaria medicagenia. The synthesis of 1 utilizes a Claisen-Schmidt condensation between 2,4-dihydroxy-3,5-C-diprenyl acetophenone and 4-methoxy benzaldehyde in the presence of Ba(OH)2 to yield the unusual chalcone 5 that contains a nine-membered ether ring. Further prenylation of 5 with 1-bromo-3-methylbut-2-ene and its subsequent demethylation with BBr3 gave munchiwarin (1).
