Synthesis of neamine-carboline conjugates for RNA binding and their antibacterial activities

Three types of neamine-β-carboline conjugates were synthesized in good yields by the coupling of neamine and β-carboline-3-carboxylic acids using aliphatic diamine as a linker. The binding properties of these conjugates to 16S rRNA and 18S rRNA were evaluated by surface plasmon resonance (SPR), showing that some conjugates had stronger binding affinities than neamine. In vitro antimicrobial activities were also evaluated and the results showed that some synthetic compounds exhibited better antibacterial activities than neamine. The preliminary structure-activity relationship was discussed. The present experimental data demonstrated that synthetic neamine-carboline conjugates might hold the potential as new antibiotics.     

Synthesis of novel benzoxaborole-containing phenylalanine analogues

The synthesis of novel benzoxaborole-containing phenylalanine analogues 2 and 3 has been developed. The key steps involve the preparation of appropriate precursors from the readily available amino acids and the formation of benzoxaborole ring directly in the corresponding amino acid fragment. The resulting compounds 2-3 show improved water solubility at physiological pH, suggesting their potential use as boron delivery agents for boron neutron capture therapy.     

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.     

Synthesis of bengamide E analogues and their cytotoxic activity

A series of bengamide E analogues were prepared from the corresponding polyketide chain and amino acids via amide coupling reactions. Opening of the polyketide chain lactone ring with α-aminolactams was successfully achieved under microwave irradiation in the presence of sodium 2-ethyl hexanoate. A cytotoxic activity evaluation against a panel of cancer cell lines (KB, HepG-2, Lu-1, MCF-7, HL-60 and Hela) indicated that the 2′R analogues were generally more cytotoxic than the 2′S analogues. Additionally, several analogues exhibited selective inhibition against various cancer cell lines: compounds 32a and 32b selectively inhibited MCF-7 cells, while 33b and 35b were more sensitive toward Lu-1 and HepG-2, respectively. Notably, some of the synthetic analogues possess cytotoxic activities with IC₅₀ values less than 1 µM.     

Liquid exclusion-adsorption chromatography: new technique for isocratic separation of nonionic surfactants. I. Retention behaviour of fatty alcohol ethoxylates

A new technique of liquid chromatography is described, which allows a baseline separation of fatty alcohol ethoxylates with 15–20 ethylene oxide units under isocratic conditions. The new method is based on a combination of two different chromatographic modes for the individual structural units: size exclusion for the poly(oxyethylene) chain and adsorption interaction for the hydrophobic end fragments. A theory is provided for this mixed exclusion–adsorption mode of liquid chromatography. Chromatographic data are found to be in a good agreement with this theory.     

Synthesis of novel analogues of antimycin A3

Four novel analogues of antimycin A₃, 1a-d, were synthesized in good overall yields.     

Synthesis, pharmacokinetics and in vivo antifungal activity of the novel water-soluble prodrugs of itraconazole analogue YL-24

To improve the aqueous solubility of an itraconazole analogue,compound 1(YL-24),a series of novel prodrugs were synthesized.Among these prodrugs,the phosphate disodium salt compound 7 exhibited excellent aqueous solubility(9.8 mg/mL) at near-neutral pH and sufficient stability in buffer solutions, along with favorable pharmacokinetic profiles.In particular,compounds 1 and 7 provided moderate survival efficacy in murine systemic Candida albicans SC5314 infection model,but their efficacy was weaker than that of fluconazole.     

Synthesis of febrifuginol analogues and evaluation of their biological activities

A new series of febrifuginol analogues was prepared from l-glutamic acid. An antimalarial activity evaluation against chloroquine-sensitive (T96) and chloroquine-resistant (K1) Plasmodium falciparum indicated that all the tested compounds had very strong inhibitory activity. Compounds 4 and 17b′ were inactive against KB, MCF7, HepG2 and LU1 cell lines even at a concentration of 100 μM, while they exhibited significant inhibition towards P. falciparum. Comparison of the antimalarial activity and the cytotoxic properties revealed that the 2′S isomers were more active than the corresponding 2′R isomers for this series of febrifuginol analogues, indicating that the C-2′ position is critical for the biological activity of this class of compounds.     

Synthesis and biological evaluation of 20-hydroxytriptonide and its analogues

20-Hydroxytriptonide was synthesized from readily accessible l-abietic acid in 22 linear steps, which features a Barton reaction carried out under air atmosphere to install the C20-hydroxy group. Meanwhile, we also synthesized (5R)-5-hydroxytriptolide's probable metabolite product. Preliminary structure–activity relationship studies revealed that C20-angular methyl group might play a key role in maintaining the electronic properties of the whole molecule, which was essential for retaining the cytotoxic activity and might easily and inevitably be affected by the introduction of a new group.     

Synthesis and biological evaluation of oxoapratoxin E and its C30 epimer

30R- and 30S-oxazoline analogues of apratoxin E have been prepared with late-stage formation of an oxazoline ring. These two compounds have a potent inhibitory effect on HCT-116 cell proliferation with IC₅₀ values of 345 and 638 nM, respectively. These results suggest that apratoxin E oxazoline bioisosteres are approximately 6-fold less potent than their thiazoline parent compounds. A positive impact of the 30R conformation on antiproliferative activity was also observed, with approximately 2-fold enhancement when compared to the 30S epimer.     

P[(S,S,S)-CH3NCH(CH2Ph)CH2]3N: a new C3-symmetric enantiomerically pure proazaphosphatrane

A new approach for the synthesis of C₃-symmetric proazaphosphatranes with chirality at the bridging methylene positions is reported.     

Synthesis of phosphatidylcholine analogues derived from glyceric acid: a new class of biologically active phospholipid compounds

Synthesis of a new class of phosphatidylcholine analogues derived from glyceric acid is reported for spectroscopic studies of phospholipases and the conformation of phospholipid side-chains in biological membranes, using fluorescence resonance energy transfer (FRET) techniques.     

Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method. The results showed that some of the compound had higher antitumor activity than iritecan.     

Synthesis and Incorporation of k2U into RNA

Lysidine (k²C) is one of the most modified pyrimidine RNA bases. It is a cytidine nucleoside, in which the 2-oxo functionality of the heterocycle is replaced by the ϵ-amino group of the amino acid lysine. As such, lysidine is an amino acid-containing RNA nucleoside that combines directly genotype (C-base) with phenotype (lysine amino acid). This makes the compound particularly important in the context of theories about the origin of life and here especially for theories that target the origin of translation. Here, we report the total synthesis of the U-derivative of lysidine (k²U), which should have the same base pairing characteristics as k²C if it exists in the isoC-like tautomeric form. To investigate this question, we developed a phosphoramidite building block for k²U, which allows its incorporation into RNA strands. Within RNA, k²U can base pair with the counter base U and isoG, confirming that k²U prefers an isoC-like tautomeric structure that is also known to dominate for k²C. The successful synthesis of a k²U phosphoramidite and its use for RNA synthesis now paves the way for the preparation of a k²C phosphoramidite and RNA strands containing k²C.     

二茂铁基三烯酮类姜黄素类似物的合成、晶体结构及电化学性质

以不同取代基的肉桂醛和二茂铁为起始原料,经Vilsmeier-Haack甲酰化反应、Claisen-Schmidt等反应合成5种新型二茂铁基三烯酮类姜黄素类似物,其结构经¹H NMR、¹³C NMR和HRMS(ESI-TOF)表征,并用X-ray单晶衍射确定了5d的晶体结构,其构型为反式构型,电化学研究表明化合物5a具有较高氧化还原活性。     

Synthesis and bioluminescence of electronically modified and rotationally restricted colour-shifting infraluciferin analogues

Synthetic nIR emitting luciferins can enable clearer bioluminescent imaging in blood and tissue. A limiting factor for all synthetic luciferins is their reduced light output with respect to D-luciferin. In this work we explore a design feature of whether rigidification of an exceptionally red synthetic luciferin, infraluciferin, can increase light output through a reduction in the degrees of freedom of the molecule. A rigid analogue pyridobenzimidazole infraluciferin was prepared and its bioluminescence properties compared with its non-rigid counterpart benzimidazole infraluciferin, luciferin, infraluciferin and benzimidazole luciferin. The results support the concept that synthetic rigidification of π-extended luciferins can increase bioluminescence activity while maintaining nIR bioluminescence.     

Effect of salt additives on partition of nonionic solutes in aqueous PEG-sodium sulfate two-phase system

Partition of 12 nonionic organic compounds in aqueous PEG-8000-Na(2)SO(4) two-phase system was examined. Effects of four salt additives (NaCl, NaSCN, NaClO(4), and NaH(2)PO(4)) in the concentration range from 0.027 up to ca. 1.9 M on binodal curve of PEG-sulfate two-phase system and solute partitioning were explored. It was found that different salt additives at the relatively high concentrations display different effects on both phase separation and partition of various nonionic solutes. Analysis of the results indicates that the PEG-Na(2)SO(4) ATPS with the up to 0.215 M NaCl concentration may be viewed as similar to the ATPS without NaCl in terms of the Collander equation's predictive ability of the partitioning behavior of nonionic compounds. All ATPS with each of the salt additive used at the concentration of 0.027 M may be viewed as similar to each other as the Collander equation holds for partition coefficients of nonionic solutes in these ATPS. Collander equation is valid also for the compounds examined in the ATPS with additives of NaSCN and NaClO(4) at the concentrations up to 0.215 M. The observed similarity between these ATPS might be explained by the similar effects of these two salts on the water structure. At concentrations of the salt additives exceeding the aforementioned values, different effects of salt additives on partitioning of various nonionic solutes are displayed. In order to explain these effects of salt additives it is necessary to examine the intensities of different solute-solvent interactions in these ATPS within the framework of the so-called Linear Solvation Energy Relationship (LSER) model.     

Synthesis of tanshinone ⅡA analogues and their inhibitory activities against Cdc25 phosphatases

Two series of tanshinone IIA derivatives were synthesized and evaluated for their antitumor activities as Cdc25 phosphatase inhibitors. Most of them demonstrated potent Cdc25 inhibitory activity and powerful cytotoxicity against A549 tumor cell line, producing IC₅₀ values in very low micromolar range. At last, the preliminary SAR was discussed.     

Synthesis and fungicidal activity of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines

A number of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines were synthesized.The structures of these new compounds were confirmed by ~1H NMR,IR and elemental analysis.Biological evaluation in the greenhouse showed several compounds have good fungicidal activities at 25 mg/L.