ABSTRACT
Fourteen undescribed monoterpenoid indole alkaloids, voacafrines A-N, along with 7 known monoterpenoid indole alkaloids were isolated from the seeds of Voacanga africana Stapf. Among them, voacafrines A-G were aspidosperma-aspidosperma type bisindole alkaloids, while voacafrines H-N were aspidosperma-type monomers. Their structures and absolute configurations were elucidated by a combination of NMR, MS, and ECD analyses. Voacafrines A-C were characterized by an acetonyl moiety at C-5', while voacafrine H possessed a methoxymethyl moiety at C-14 within aspidosperma-type alkaloids. The acetylcholinesterase (AChE) inhibitory activity and cytotoxicity of voacafrines A-N were evaluated. Voacafrines A-C and E-G were bisindole alkaloids that exhibited AChE inhibitory activity with IC50 values of 4.97-33.28 µM, while voacafrines I and J were monomers that showed cytotoxicity against several human cancer cell lines with IC50 values of 4.45-7.49 µM.
Subject(s)
Aspidosperma , Secologanin Tryptamine Alkaloids , Voacanga , Indole Alkaloids/pharmacology , Molecular Structure , Secologanin Tryptamine Alkaloids/pharmacologyABSTRACT
Twenty-one aspidosperma-aspidosperma alkaloids, including the new tabernaesines A-J (1-9), were obtained from Tabernaemontana pachysiphon. The structures and absolute configurations were elucidated using HRMS and NMR experiments. Compounds 1-9 possessed a rare spiro heterocycle moiety between the monomeric units, while compounds 4 and 5 were characterized by an indole ring fused with an (N,N-diethyl)methyl amino group. Compounds 1, 5-7, 15, and 16 exhibited moderate cytotoxic potency against various human cancer cell lines at IC50 2.5-9.8 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Indole Alkaloids/isolation & purification , Tabernaemontana/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Spectrum Analysis/methodsABSTRACT
Twenty-two diterpenoids (1-22), including two new ones (1, a tigliane-type diterpenoid and 8, an abietane-type diterpenoid) were isolated from the roots of Euphorbia fischeriana Steud. Among them, compounds 4, 7, 12, 14-16, 19-21 are isolated from this plant for the first time. Their structures were elucidated through extensive 1D, 2D NMR and the HRESIMS data. The 13C data of 4 is hereby presented for the first time. The macrocyclic diterpenes 1 and 2 showed marked enhancement of lysosomal biosynthesis after evaluation using lysoTracker staining method.
Subject(s)
Diterpenes/chemistry , Diterpenes/pharmacology , Euphorbia/chemistry , Lysosomes/drug effects , Abietanes/chemistry , Diterpenes/isolation & purification , Drug Evaluation, Preclinical , HeLa Cells , Humans , Lysosomes/metabolism , Magnetic Resonance Spectroscopy , Molecular Structure , Oxygen/chemistry , Phorbol Esters/chemistry , Plant Roots/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
A sensitive and rapid LC-MS/MS method has been developed and validated for quantifying swertianolin in rat plasma using rutin as an internal standard (IS). Following liquid-liquid extraction with ethyl acetate, chromatographic separation for swertianolin was achieved on a C18 column with a gradient elution using 0.1% formic acid as mobile phase A and acetonitrile as mobile phase B at a flow rate of 0.3 mL/min. The detection was performed on a tandem mass spectrometer using multiple reaction monitoring via an electrospray ionization source and operating in the negative ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were 435.1/272.0 for swertianolin and 609.2/300.1 for IS. The lower limit of quantitation was 0.5 ng/mL within a linear range of 0.5-500 ng/mL. Intra-day and inter-day precision was less than 6.8%. The accuracy was in the range of -13.9 to 12.0%. The mean recovery of swertianolin was >66.7%. The proposed method was successfully applied in evaluating the pharmacokinetics of swertianolin after an oral dose of 50 mg/kg Swertia mussotii extract in rats.