ABSTRACT
Man has relied on plants as a source of medicinal agents for centuries. Today, with the specter of antibiotic resistance, emerging infectious diseases, and cancers, phytochemicals continue to provide new structural leads for the chemotherapeutic industry. A number of triterpenoids have shown promise as antineoplastic agents. Members of the cycloartane, lupane, ursane, oleanane, friedelane (especially quinone methides), dammarane, cucurbitacin, and limonoid triterpenoids, have demonstrated anti-proliferative activity on various cancer cell lines. This review covers the recent developments regarding antineoplastic/cytotoxic triterpenoids, excluding saponins, from higher plants.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Plants/chemistry , Triterpenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Drug Screening Assays, Antitumor , Humans , Saponins/chemistry , Saponins/isolation & purification , Saponins/pharmacology , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purification , Tumor Cells, Cultured/drug effectsABSTRACT
Two new hydrolyzable tannins, isoterchebulin (1) and 4,6-O-isoterchebuloyl-D-glucose (2), together with six known tannins, 3-8, were isolated from the bark of Terminalia macroptera. Their structures were elucidated by extensive 1D and 2D NMR studies, MS, and chemical transformations. Biological activities of all compounds were evaluated against the snail Biomphalaria glabrata, the bacteria Bacillus subtilis and Pseudomonas fluorescens, the nematode Caenorhabditis elegans, and four cancer cell lines (Hep G2, MCF-7/S, MDA-MB-231, and 5637 cells). All compounds except 3 showed antimicrobial activities against B. subtilis (MIC 8-64 microg/mL), whereas only 1 was active against C. elegans (100 microg/mL) and B. glabrata(LC(100) = 60 microg/mL). 3 and 8 were toxic against 5637 cells with LC(50) = 84.66 and 41.40 microM, respectively.
Subject(s)
Glucose/isolation & purification , Hydrolyzable Tannins , Plants, Medicinal/chemistry , Tannins/isolation & purification , Trees/chemistry , Africa , Animals , Anthelmintics/chemistry , Anthelmintics/isolation & purification , Anthelmintics/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Bacillus subtilis/drug effects , Biomphalaria/drug effects , Caenorhabditis elegans/drug effects , Glucose/analogs & derivatives , Glucose/chemistry , Glucose/pharmacology , Magnetic Resonance Spectroscopy , Molluscacides/chemistry , Molluscacides/isolation & purification , Molluscacides/pharmacology , Pseudomonas fluorescens/drug effects , Tannins/chemistry , Tannins/pharmacology , TilapiaABSTRACT
The crude dichloromethane bark extract of Salacia petenensis (Hippocrateaceae) from Monteverde, Costa Rica, shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of tingenone and netzahualcoyonol as the biologically active materials. Also isolated from the extract were 3-methoxyfriedel-2-en-1-one (a new natural product) and 29-hydroxyfriedelan-3-one. The structures of these compounds were elucidated on the basis of NMR spectral analysis. Molecular orbital calculations have been carried out using the semi-empirical PM3 and Hartee-Fock 3-21G ab initio techniques on the quinone-methide nortriterpenoids tingenone and netzahualcoyonol, as well as on the nucleotide bases adenine, guanine, cytosine, and thymine. The molecular orbital calculations suggest that a possible mode of cytotoxic action of quinone-methide triterpenoids involves quasi-intercalative interaction of the compounds with DNA followed by nucleophilic addition of the DNA base to carbon-6 of the triterpenoid.
Subject(s)
Indolequinones , Indoles/isolation & purification , Quinones/isolation & purification , Rosales/chemistry , Triterpenes/isolation & purification , Indoles/chemistry , Models, Molecular , Molecular Structure , Quinones/chemistry , Triterpenes/chemistryABSTRACT
The synthesis of a series of diacetylenic compounds related to the natural product falcarindiol has been carried out. Unsymmetrical diacetylenes were prepared by a modification of the Cadiot-Chodkiewicz coupling reaction, while a Glaser coupling was used to prepare symmetrical diacetylenes. These compounds have been tested for in vitro cytotoxic activity against Hep-G2, and H-4-II-E cell lines. Diacetylenes with additional unsaturation at C-1, 2, appended with hydroxyl groups at C-3 and C-8, or with long hydrophobic chains, exhibited IC50 values in the micromolar range.
Subject(s)
Antineoplastic Agents/chemical synthesis , Fatty Alcohols/chemical synthesis , Antineoplastic Agents/pharmacology , Diynes , Drug Screening Assays, Antitumor , Fatty Alcohols/pharmacology , Humans , Plants, Medicinal/chemistry , Tumor Cells, CulturedSubject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Trees/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Chromatography , Costa Rica , Furocoumarins/chemistry , Furocoumarins/isolation & purification , Furocoumarins/pharmacology , Magnetic Resonance Spectroscopy , Methoxsalen/chemistry , Methoxsalen/isolation & purification , Methoxsalen/pharmacology , Plant Extracts/chemistry , Plant Stems/chemistry , Quinolines/chemistry , Quinolines/isolation & purification , Quinolines/pharmacology , Sitosterols/chemistry , Sitosterols/isolation & purification , Sitosterols/pharmacology , Tumor Cells, Cultured , X-Ray DiffractionABSTRACT
The crude chloroform bark extract of Syncarpia glomulifera (Myrtaceae) shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of oleanolic acid-3-acetate, ursolic acid-3-acetate and betulinic acid. The relatively large abundance (10% of the crude extract) and high degree of activity of betulinic acid are responsible for the bioactivity of the crude bark extract.
Subject(s)
Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Triterpenes/pharmacology , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Triterpenes/chemistry , Tumor Cells, CulturedABSTRACT
The leaf essential oil of an undescribed species of Myrcianthes has been obtained from Monteverde, Costa Rica. The essential oil exhibits in vitro cytotoxic activity against Hep-G2 and SK-Mel-28 human tumor cell lines. A GC/MS analysis shows the essential oil to be composed of 2-heptanol, alpha-pinene, beta-pinene, limonene, cineole, and alpha-terpineol, alpha-Pinene, beta-pinene, and limonene account for the cytotoxic activity of the leaf essential oil of Myrcianthes sp. nov. "black fruit".
Subject(s)
Oils, Volatile/toxicity , Trees , Animals , Artemia/drug effects , Costa Rica , Humans , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Plant Leaves , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The crude chloroform bark extract of Piper caninum (Piperaceae) exhibits antibacterial activity against the Gram-positive bacteria, Bacillus cereus, Staphylococcus aureus, and Streptococcus pneumoniae. The antibacterial agents in this extract have been isolated using bioactivity-directed chromatographic techniques and identified by NMR spectroscopy as (+)-bornyl p-coumarate and bornyl caffeate. A single-crystal X-ray structure has been carried out on (+)-bornyl p-coumarate. The compound crystallizes in the orthorhombic space group P2(1)2(1)2(1) (#19) with a = 12.659(4), b = 13.281(4), and c = 10.177(3) A. Fullmatrix least-squares refinement converged at R = 0.047, and Rw = 0.058.