PubMed Health⌕ Search

Biomedical subjects

Biao Yu

Publications and source records attributed to Biao Yu.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis and cytotoxicities of dioscin derivatives with decorated chacotriosyl residues.

Two series of dioscin derivatives (4a-o and 5a-o) with selected modifications at the 6' and 4''' positions of the chacotriosyl residue, respectively, were synthesized. All the 6'-N-acyl-dioscin derivatives did not show considerable inhibitory activities at 10 microM, while most of the 4'''-O-(2-N-acyl)ethyl-dioscin derivatives behaved as potent as dioscin, against the growth of tumor cells.

Cell Line, Tumor↗
PubMed2006

Synthesis of 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative structure of aescuflavoside A from the seeds of Aesculus chinensis.

3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative flavonal glycoside named aescuflavoside A, isolated from the seeds of Aesculus chinensis, is synthesized via regioselective glycosylation of 7-O-benzyltamarixetin with glycosyl bromides under phase-transfer-catalyzed conditions.

Aesculus↗
PubMed2005

OSW saponins: facile synthesis toward a new type of structures with potent antitumor activities.

[reaction: see text] OSW saponins, featuring a 16beta,17alpha-dihydroxycholest-22-one aglycon and an acylated beta-D-xylopyranosyl-(1-->3)-alpha-L-arabinopyranosyl residue attached to the 16-hydroxyl group, have recently been discovered from a group of lily plants, which show potent antitumor activities with a novel mechanism of action. This paper describes an aldol approach to the stereoselective construction of the 16alpha,17alpha-dihydroxycholest-22-one structure from 16alpha-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketone side chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxy function, has been explored and accomplished. In particular, the present route was found convenient for the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogue of OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a linear eight-step sequence and in 26% overall yield. Analogues with a variety of modified side chains were prepared, via aldol condensation with propionates of varying length, thiopropionate, and acetate (for preparation of 68-75) or via aminolysis of the 22,16-lactone 26 (for preparation of the 23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at the final stage from C22-allyl ester 70. Valuable structure-activity relationships (SAR), together with the practical synthetic approach, have thus been provided to set a new stage for further studies on this new type of antitumor structures.

Antineoplastic Agents↗
PubMed2005

Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft.

Paris polyphylla is a traditional Chinese Medical herb that has been used in treating cancer for thousands of year. Without studies on the anticancer effects of Paris polyphylla being initiated before, we have first studied the component of Paris polyphylla and have spotted out a steroidal saponin, polyphyllin D. As long as the chemical structure and the improved synthesis of polyphyllin D were ascertained, both in vitro to in vivo studies were performed. It was found that treatment of MCF-7 and MDA-MB-231 cells with polyphyllin D resulted in the inhibition of viability and induction of apoptosis in a dose-dependent manner, with an IC50 of 5 microM and 2.5 microM, respectively, after 48 hours of incubations. Apoptosis of MCF-7 and MDA-MB-231 cells by polyphyllin D was evidenced by the occurrence of DNA fragmentation, formation of a hypodiploid peak in the cell cycle analysis, phosphatidyl-serine externalization and a late loss of membrane integrity. Mechanistically, polyphyllin D dissipates the mitochondrial membrane potential, induces a downregulation of anti-apoptotic Bcl-2 expression and an up-regulation of pro-apoptotic Bax expression, and activates caspase-9. These results suggest that polyphyllin D elicits apoptosis through mitochondria dysfunction. In vivo study demonstrated that daily administration of polyphyllin D (2.73 mg/kg body weight) through intravenous injection for ten days in nude mice bearing MCF-7 cells effectively reduced tumor growth for 50% in terms of tumor weight and size, given no significant toxicity in heart and liver to the host. All these findings provide novel insights that polyphyllin D could serve as a candidate in breast cancer treatment.

Animals↗
PubMed2005

Total synthesis of CRM646-A and -B, two fungal glucuronides with potent heparinase inhibition activities.

[reaction: see text] CRM646-A (1) and -B (2), two fungal glucuronides with a dimeric 2,4-dihydroxy-6-alkylbenzoic acid (orcinol p-depside) aglycone showing significant heparinase and telomerase inhibition activities, were synthesized for the first time. The successful approach involved construction of the phenol glucuronidic linkage, via coupling of the orsellinate derivative 27 with glucuronate bromide 7, before assembly of the phenolic ester linkage in the depside aglycone. Attempts via direct glycosylation of the depside aglycone derivatives were not successful.

Acremonium↗
PubMed2005

Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2.

OSW-1 is a new member of cholestane saponin family, which is cytotoxic against several types of malignant cells. We reported herein that OSW-1 induced apoptosis of mammalian cells in a concentration- and time-dependent manner. The drug-induced apoptosis was mediated through the mitochondrial pathway, involving the cleavage of Bcl-2. This drug-induced Bcl-2 cleavage in Chinese hamster ovary (CHO) cells could be suppressed either by dominant-negative caspase-8 or by a caspase-8 inhibitor, suggesting that the Bcl-2 cleavage is dependent on caspase-8. In contrast, the Bcl-2 cleavage was independent of caspase-3 activity. The inhibition of caspase-8 activity also resulted in the reduction of apoptotic cells, indicating that Bcl-2 cleavage induced by caspase-8 promotes the progression of apoptosis. The involvement of the caspase-8 activity in the processes of the OSW-1-induced apoptosis was further examined by using caspase-8-deficient Jurkat T cells. It was found that the caspase-8-deficient cells were resistant to OSW-1-induced Bcl-2 cleavage or apoptosis. Furthermore, the small subunit of caspase-8 was found to interact with Bcl-2 as determined by yeast two-hybrid and coimmunoprecipitation assays. Overexpression of caspase-8 small subunit reduced the cleavage of Bcl-2 and inhibited the apoptosis induced by OSW-1. Taken together, these results demonstrate that OSW-1 is capable of inducing apoptosis in mammalian cells, in which the caspase-8-dependent cleavage of Bcl-2 plays an important role.

Animals↗
PubMed2005

Kinetic analysis of an efficient DNA-dependent TNA polymerase.

alpha-l-Threofuranosyl nucleoside triphosphates (tNTPs) are tetrafuranose nucleoside derivatives and potential progenitors of present-day beta-d-2'-deoxyribofuranosyl nucleoside triphosphates (dNTPs). Therminator DNA polymerase, a variant of the 9 degrees N DNA polymerase, is an efficient DNA-directed threosyl nucleic acid (TNA) polymerase. Here we report a detailed kinetic comparison of Therminator-catalyzed TNA and DNA syntheses. We examined the rate of single-nucleotide incorporation for all four tNTPs and dNTPs from a DNA primer-template complex and carried out parallel experiments with a chimeric DNA-TNA primer-DNA template containing five TNA residues at the primer 3'-terminus. Remarkably, no drop in the rate of TNA incorporation was observed in comparing the DNA-TNA primer to the all-DNA primer, suggesting that few primer-enzyme contacts are lost with a TNA primer. Moreover, comparison of the catalytic efficiency of TNA synthesis relative to DNA synthesis at the downstream positions reveals a difference of no greater than 5-fold in favor of the natural DNA substrate. This disparity becomes negligible when the TNA synthesis reaction mixture is supplemented with 1.25 mM MnCl(2). These results indicate that Therminator DNA polymerase can recognize both a TNA primer and tNTP substrates and is an effective catalyst of TNA polymerization despite changes in the geometry of the reactants.

Base Sequence↗
PubMed2005

Synthesis of alpha-L-threofuranosyl nucleoside triphosphates (tNTPs).

[structure: see text] The alpha-l-threofuranosyl nucleoside triphosphates of T, G, and D (tTTP, tGTP, and tDTP) were synthesized from the described 2'-O-DMT-protected derivatives using the Eckstein method, while the corresponding C derivative (tCTP) was prepared from the 2'-O-acetyl derivative. The prepared alpha-l-threofuranosyl nucleoside triphosphates, despite being one carbon shorter than the native 2'-deoxyfuranosyl nucleoside triphosphates, are effective substrates for selected DNA polymerases.

DNA-Directed DNA Polymerase↗
PubMed2005

An in vitro selection system for TNA.

(3'-2')-alpha-l-Threose nucleic acid (TNA) is an unnatural polymer that possesses the rare ability to base-pair with RNA, DNA, and itself. This feature, coupled with its chemical simplicity, makes TNA of interest as a possible progenitor of RNA during the early history of life. To evaluate the functional potential of TNA, we have developed a system for the in vitro selection of TNA. We identified the Therminator DNA polymerase as a remarkably efficient DNA-dependent TNA polymerase capable of polymerizing more than 50 tNTPs. We have also developed a method of covalently linking a DNA template to the TNA strand that it encodes, thus obviating the need for a TNA-dependent DNA polymerase during cycles of selection.

Archaeal Proteins↗
PubMed2005

Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells.

In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl alpha-L-rhamnopyranosyl-(1-->2)-(alpha-L-arabinofuranosyl)-(1-->4)]-[beta-D-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (DeltaPsim), generation of H2O2, as well as release of cytochrome c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

Apoptosis↗