ABSTRACT
Phytochemical investigation of Ferula seravschanica afforded seven new compounds, including three new bicyclic-type sesquiterpene coumarins (1-3), two new monocyclic-type sesquiterpene coumarins (16-17), two new phenylpropanoids (23-24) as well as twenty-two known compounds (4-15, 18-22, and 25-29). The structures of new compounds were determined by HRESIMS, NMR, ECD calculations, and X-ray single-crystal diffraction analysis. Furthermore, crude EtOAc extract and separated fractions (F1-F12) possessed cytotoxic activity against four human tumor cell lines (HT-29, DU145, HeLa, and Jurkat). Subsequently, we examined Jurkat inhibitory activity of isolated compounds. Compound 12 significantly inhibited the proliferation of the leukemia cells with IC50 value of 2.50 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Coumarins/pharmacology , Ferula/chemistry , Sesquiterpenes/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Coumarins/isolation & purification , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Roots/chemistry , Sesquiterpenes/isolation & purification , TajikistanABSTRACT
Seven new diterpenoids, euphorantones A-D (1, 3, 6, and 10), 8,12,13-epi-3,7,12-O-triacetyl-8-O-(2-methylbutanoyl)-ingol (9), 8,12,13-epi-3,12-O-diacetyl-7-O-benzoyl-8-methoxyingol (11), 2,3-epi-7,12-diacetate-8-benzoate-ingol (12), together with eighteen known compounds (2, 4-5, 7-8, and 13-25), were isolated from the aerial parts of Euphorbia antiquorum L.. The structures of new compounds 1, 3, 6, and 9-12 were elucidated by extensive spectroscopic analyses. The absolute configurations of new compounds were assigned using X-ray diffraction, Rh2(OCOCF3)4-induced CD spectrum, and confirmed through comparison of the calculated and experimental 13C NMR and electronic circular dichroism (ECD) data. Compounds 1-25 were evaluated for their inhibition of RANKL-induced osteoclastogenesis. Compound 1 showed the most potent inhibition of RANKL-induced osteoclastogenesis with IC50 value of 0.3⯵M. It inhibited NFAT transcript activity and osteoclast related genes TRAcP, CTSK, and NFATc1 expression.
Subject(s)
Diterpenes/pharmacology , Drug Discovery , Euphorbia/chemistry , Osteogenesis/drug effects , Plant Extracts/pharmacology , RANK Ligand/antagonists & inhibitors , Animals , Cell Survival/drug effects , Cells, Cultured , Crystallography, X-Ray , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Mice , Mice, Inbred C57BL , Models, Molecular , Molecular Structure , Osteoclasts/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RANK Ligand/metabolism , Structure-Activity RelationshipABSTRACT
Three new cembrane-type diterpenoids, deheiculatins M-O (1-3), together with five known analogues (4-8), were isolated from the twigs of Macaranga pustulata King ex Hook. The structures of new compounds 1-3 were elucidated by extensive spectroscopic analyses, modified Mosher's method, and the experimental and calculated electronic circular dichroism (ECD) experiments. All the isolates were evaluated for their cytotoxicity on three human cancer cell lines (CNE1, CNE2, and HCT 116), and all of them showed weak cytotoxicity (IC50â¯>â¯20⯵M).
