Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives.

A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d-galactopyranoside 8b, epipodophyllotoxin α-d-arabinopyranoside 8e, and podophyllotoxin ß-d-glucopyranoside 11a show the highest potency of anticancer activity with their IC50 values ranging from 0.14 to 1.69µM. Structure activity relationship analysis indicates that the type of glycosidic linkage, the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4'-position (OH vs OCH3) can all have significant effect on the potency of their anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin, suggesting their potential as anticancer agents for further development.

Design, synthesis, and cytotoxicity of perbutyrylated glycosides of 4ß-triazolopodophyllotoxin derivatives.

A series of novel perbutyrylated glycosides of 4ß-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC50 values ranging from 0.49 to 6.70 µM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold.

Daphnane-type diterpenoid glucosides and further constituents of Euphorbia pilosa.

Phytochemical investigation of whole plants of Euphorbia pilosa led to the isolation and identification of two new daphnane-diterpenoid glucosides, euphopilosides A and B (1 and 2, resp.), and a new ent-abietane, euphopilolide (3), together with eight known compounds. Compounds 1 and 2 are the first daphnane-type diterpenoid glycosides. Their structures were elucidated by a combination of 1D- and 2D-NMR, and MS analyses, and acid hydrolysis. Compounds 1-9 were evaluated for their in vitro cytotoxicities against five human tumor cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480. Compound 7 showed moderate inhibitory activity against all five cell lines.

Meroterpenoid pigments from the basidiomycete Albatrellus ovinus.

Eight grifolin derivatives, involving three new monomers, albatrelins A-C (1-3), three novel dimers (meroterpenoid pigments), albatrelins D-F (4-6), and two known ones, 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methyl-3-penten-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (7) and confluentin (8), were isolated from Albatrellus ovinus. Their structures were established by extensive spectroscopic analysis. The absolute configurations of compounds 2-4 were determined as 9R by comparing their optical rotations with data reported in the literature. Albatrelin F (6) was isolated as a pair of C-2' tautomers with a ratio of 1.3:1. Confluentin (8) showed weak cytotoxicity against four human tumor cell lines, HL-60, SMMC-7712, A-549, and MCF-7, in vitro.

Two new diterpenoids from Excoecaria acerifolia.

A new tigliane diterpenoid, acerifolin A (1), and a new isopimarane diterpenoid, acerifolin B (2), together with two known compounds, were isolated from Excoecaria acerifolia. Their structures were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. All of the compounds were evaluated for cytotoxicity against five human cancer cell lines with cisplantin as a positive control.

Synthesis and anticancer activity of glucosylated podophyllotoxin derivatives linked via 4ß-triazole rings.

A series of 4ß-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC50 values ranging from 0.59 to 2.90 µM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue.

Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata.

Five new hexacyclic monoterpenoid indole alkaloids, rauvovertine A (1), 17-epi-rauvovertine A (2), rauvovertine B (3), 17-epi-rauvovertine B (4), and rauvovertine C (5) together with 17 known analogues were isolated from the stems of Rauvolfia verticillata. Compounds 1/2 and 3/4 were obtained as C-17 epimeric mixtures due to rapid hemiacetal tautomerism in solution. The structures of 1-5 were established by spectroscopic analysis and with the aid of molecular modeling. The new alkaloids were evaluated for their cytotoxicity in vitro against human tumor HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines.

Synthesis and Anticancer Activity of 4ß-Triazole-podophyllotoxin Glycosides.

A series of novel 4ß-triazole-podophyllotoxin glycosides were synthesized by utilizing the Click reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assay shows that most of these compounds show weak cytotoxicity. It was observed that compound 16 shows the highest activity with IC50 values ranging from 2.85 to 7.28 µM, which is more potent than the control drugs etoposide and cisplatin against four of five cancer cell lines tested. Compound 16 is characterized with an α-D-galactosyl residue directly linked to the triazole ring and a 4'-OH group on the E ring of the podophyllotoxin scaffold. HPLC investigation of representative compound indicates that incorporation of a sugar moiety seems to improve the chemical stability of the podophyllotoxin scaffold.

Identification and Cytotoxic Activities of Two New Trichothecenes and a New Cuparane-Type Sesquiterpenoid from the Cultures of the Mushroom Engleromyces goetzii.

Engleromyces goetzii is a traditional medicinal mushroom that is widely used to treat infection, inflammation and cancer in Tibet, Sichuan and Yunnan provinces of China. Two new trichothecenes, engleromycones A and B (1 and 2), one new cuparane-type sesquiterpenoid named infuscol F (11), eight known trichothecene analogs, sambucinol (3), 3-deoxysambucinol (4), trichothecolone (5), trichodermol (6), 8-deoxytrichothecin (7), trichothecin (8), trichothecinol B (9) and trichothecinol A (10), and one known cyclopentanoid sesquiterpene cyclonerodiol (12) were isolated from the cultures of E. goetzii. The new compounds were elucidated through spectroscopic analyses. The anticancer effects of trichothecenes 1-10 were examined in the HL-60, SMMC-7721, A549, MCF-7, and SW-480 human cancer cell lines using an MTT assay. Trichothecinol A (10) significantly inhibited the growth of MCF-7 cells, with an IC50 value of 0.006 µM, which was comparable to the cytotoxic activity of the positive control, paclitaxel, indicating that trichothecinol A (10) represents a potential anticancer agent.

Nine new farnesylphenols from the basidiomycete albatrellus caeruleoporus.

Nine previously-unreported farnesylphenols, involving eight neogrifolin derivatives (1-8) and one grifolin analogue (9), together with three known compounds, were isolated from the fruiting bodies of the mushroom Albatrellus caeruleoporus. Their structures were elucidated as (S)-17-hydroxy-18,20-ene-neogrifolin (1), (S)-18,19-dihydroxyneogrifolin (2), (S)-9-hydroxy-10,22-ene-neogrifolin (3), (9S,10R)-6,10-epoxy-9-hydroxyneo grifolin (4), (9S,10R)-6,9-epoxy-10-hydroxyneogrifolin (5), (-)-13,14-dihydroxyneogrifolin (6), albatrelin G (7), albatrelin H (8), and one grifolin analogue, (S)-10-hydroxygrifolin (9), grifolin (10), neogrifolin (11), and albatrellin (12) by extensive spectroscopic analyses and chemical methods. Compounds 7 and 8 showed weak cytotoxic activity to cell lines HL-60, SMMC-7721, A-549, and MCF-7, in vitro.

Labdane diterpenoids and lignans from Calocedrus macrolepis.

Three new labdane diterpenoids, calomacrins A-C (1-3), and a new diaryl butyrolactone-type lignan, calomacrol A (8), as well as four known labdane diterpenoids and six known lignans, were isolated from the twigs and leaves of Calocedrus macrolepis. Structures of the new compounds were elucidated on the basis of their spectroscopic methods, including 1D and 2D NMR techniques. Compounds 3-14 were evaluated for cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines.