Total synthesis of chondroitin sulfate E oligosaccharides and biological study.

A total synthesis approach of CS-E oligosaccharides was established and a series of derivatives were synthesized. These oligosaccharides were evaluated for a glycosaminoglycan (GAG)-binding protein interaction against cytokines, midkine, and pleiotrophin, by surface-plasmon resonance (SPR) assay. The binding epitopes of oligosaccharides to midkine were mapped using a saturation transfer difference (STD) NMR technique. The groups on the reducing end contributed to binding affinity, and should not be ignored in biological assays. These findings contribute to the structure and activity relationship research and a foundation of understanding that will underpin potential future optimization of this class of oligosaccharides as pharmaceutical agents.

Antibacterial activities of a series of novel 5-O-(4', 6'-O-dimodified)-mycaminose 14-membered ketolides.

A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were assessed for their in vitro antibacterial activities against a panel of sensitive and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the best antibacterial activities against several macrolide-sensitive and macrolide-resistant strains. These results indicated that introducing ester to 6-OH and a small volume ether substituent to the 4-OH of mycaminose could improve the antibacterial activities of ketolides.

Synthesis and Antibacterial Activity of Novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains.

A series of novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors (18, 19) with 4″-OH of compounds 5a-c. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and compounds 21d and 21e displayed significant improvement of activities against resistant pathogens.

Synthesis and antibacterial activity of novel ketolides with 11,12-quinoylalkyl side chains.

A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.

Synthesis and antibacterial activities of some novel 17, 18-unsaturated carbonyl compounds derivated from josamycin.

Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.

Synthesis and cytotoxic activity of two steroids: icogenin aglycone analogs.

During the process of icogenin analog research, we obtained two cytotoxic steroids: compound 4 and compound 6 casually. Their in vitro antitumor activities were tested by the standard MTT assay. The results disclosed that compound 4 (IC50 = 3.65-6.90 µM) showed potential antitumor activities against HELA, KB cell lines and compound 6 (IC50 = 2.40-9.05 µM) showed potential antitumor activities against HELA, BGC-823, KB, A549, HCT-8 cell lines.

Synthesis of three OSW-1 analogs with maltose side chains bearing different protection groups.

In order to simplify the synthesis of OSW-1's disaccharide side chain and explore the structure-activity relationship of OSW-1, three 16α-O-maltose OSW-1 analogs carrying three maltose side chains bearing different protections were designed and synthesized.

Synthesis and antitumor activity of 5,6-dihydro-17-hydroxy icogenin analogs.

Four 5,6-dihydro-17-hydroxy icogenin analogs were designed and synthesized. Their in vitro antitumor activities were tested by the standard MTT assay. Compound 22 (IC(50) = 3.38-8.30 µM) and compound 23 (IC(50) = 1.90-9.69 µM) showed potential antitumor activities against the entire tested seven cancer cell lines. The SAR (structure activity relationship) research showed that the introduction of 17-hydroxy lowered the antitumor activity to an extent.

Synthesis and antibacterial activity of novel ketolides with 11,12-sulfur contained aryl alkyl side chains.

A novel series of ketolides with 11,12-sulfur contained aryl alkyl side chains were synthesized and evaluated for their antibacterial activity. These ketolides exhibited potent activity against key macrolide sensitive and resistant respiratory pathogens. The newly synthesized 9a, 9e, 9k and 9n showed a similar antimicrobial spectrum and comparable activity to telithromycin, the commercial ketolide antibacterial.

A new series of macrolide derivatives with 4''-O-saccharide substituents.

A series of novel derivatives of macrolide with 4''-O-mono- or disaccharides were synthesized. The corresponding glycosyl trichloroacetimidates were used as the donors in the glycosylations. The in vitro antibacterial activities of 7a-f and 13-16 against a panel of susceptible and resistant pathogens were tested. The modification of 4''-O-mono- or disaccharides may lead to the understanding of interaction of the macrolide and the bacterial ribosome.

[Effect of icogenin on and its mechanism in anti-metastasis of pancreatic cancer BxPC3 cells].

This study is to investigate the effect of Icogenin on and its mechanism in anti-metastasis of pancreatic cancer BxPC3 cells in vitro. Using transwell assay, the effects of Icogenin on the invasion of BxPC3 cells were measured. The abilities of cell motility and adhesion in BxPC3 cells were detected by MTT assay and wound healing assay, respectively. The MAPK signal pathway protein expressions were analyzed with Western blotting. Also, the activity of MMP2 was observed by zymography assay. Icogenin inhibited the abilities of motility, adhesion and invasion of pancreatic cancer BxPC3 cells in vitro (P < 0.05), in a dose-depended manner, and inhibited the secretion of MMP2 and phosphorylation of ERK. PD98059 and U0126 which were ERK inhibitors could suppress the abilities of invasion and metastasis of pancreatic cancer BxPC3 cells. It is concluded that Icogenin can inhibit the abilities of invasion and metastasis of pancreatic cancer in vitro by inhibiting the secretion of MMP2 and phosphorylation of ERK.

Synthesis of novel macrolide derivatives with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains and their antibacterial activity.

In an effort to find new antibiotics, a novel series of 14-membered macrolides with imidazo[4,5-b]pyridinyl sulfur contained alkyl side chains has been synthesized based on commercially available clarithromycin. Chemical transformation of hydroxy group at position C-3 afforded range of ketolides and acylides. Compared to telithromycin, compound 15a demonstrated improved in vitro activity against erythromycin-susceptible and -resistant strains.

Synthesis and antibacterial activity of 11,12-carbamate-3-O-acyl erythromycin derivatives.

A novel series of acylide derivatives have been synthesized which exhibit in vitro potency against key respiratory pathogens. Modification of position 3 was accomplished by replacing different 3-O-substituted acyl groups in the macrolide core via a facile procedure. Compounds 7a-7i were eventually yielded by the conjunction of diverse hetero-aryl side chains with the 11-N,12-O-carbamate sub-structure.

Synthesis and antibacterial activity of 4''-O-heteroarylcarbamoyl derivatives of macrolide.

A series of novel 4''-position modified macrolide derivatives has been synthesized via a facile procedure. Their in vitro antibacterial activities against constitutively erythromycin-resistant strains were evaluated. Among the derivatives tested, compound 8a which has 11,12-carbamate and 4''-O-heteroarylcarbamoyl groups was found to have potent activity against most resistant bacteria.

[Synthesis of derivatives of (9S) -9-hydroxyl-12-methylene erythromycin A and their antibacterial activity in vitro].

The derivatives of (9S)-9-hydroxyl-12-methylene erythromycin A were synthesized by using erythromycin A as a starting material. An intermediate (9S)-9,11-O-isopropylidene-6-O-allyl-2' ,4"-O-bis(benzoyl)-12,21-anhydro erythromycin A 12 was obtained. The antibacterial activity in vitro of two compounds, 6 and 11, was tested. The preliminary biological test showed that two compounds exhibited less potent antibacterial activity in vitro.

[Synthesis of derivatives of (9S)-12-methylene erythromycin and their antibacterial activity in vitro].

AIM: To synthesizs of derivatives of (9S)-12-methylene erythromycin possessed potent antibacterial activity. METHODS: Using erythromycin A as a starting material, via two intermediate compounds protected 12,21-dehydroerythromycin A and 6,7: 12,21-didehydro erythromycin A, several 9-O, 11-O-ethylidene compounds were obtained. During this process, benzyl and isopropyl have been selected as the protecting group. The structures of compounds obtained were confirmed with 13C NMR and MS-FAB. Their antibacterial activity in vitro was tested. RESULTS: Eleven derivatives of erythromycin were synthesized. Five of them were unknown compounds. CONCLUSION: The preliminary biological test showed that two target compounds exhibited less potent antibacterial activity in vitro.

[Advance in synthesis of ketolides, a new class of erythromycin derivatives].

Drug-resistance has become a challenging clinical problem. Ketolides, a new class of erythromycin derivatives, have shown promising effectiveness in killing drug-resistant bacteria. This article reviews recent development in synthesis of ketolides, with focus on the modification and synthesis of some important positions on erythromycin A cycles.

The synthesis of gracillin and dioscin: two typical representatives of spirostanol glycosides.

Two representative spirostanol saponins that have the typical structure for the sugar moiety, diosgenyl alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranoside (gracillin) and diosgenyl alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-D-glucopyranoside (dioscin), were easily synthesized by a general approach. A procedure using guanidine for the selective deblocking of acetyl while retaining benzoyl protecting groups is described.