Xiaohui Li

Dalian University of Technology, Lü-ta-shih, Liaoning, China

Are you Xiaohui Li?

Claim your profile

Publications (11)26.6 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The histone deacetylase (HDAC) family is a promising drug target class owing to the importance of these enzymes in a variety of cellular processes. Docking studies were conducted to identify novel HDAC inhibitors. Subtle modifications in the recognition domain were introduced into a series of chlamydocin analogues, and the resulting scaffolds were combined with various zinc binding domains. Remarkably, cyclo(L-Asu(NHOH)-L-A3mc6c-L-Phe-D-Pro, compound 1 b), with a methyl group at positions 3 or 5 on the aliphatic ring, exhibited better antiproliferative effects than trichostatin A (TSA) against MCF-7 and K562 cell lines. In addition to cell-cycle arrest and apoptosis, cell migration inhibition was observed in cells treated with compound 1 b. Subsequent western blot analysis revealed that the balance between matrix metalloproteinase 2 (MMP2) and tissue inhibitors of metalloproteinase 1 (TIMP1) determines the degree of metalloproteinase activity in MCF-7 cells, thereby regulating cell migration. The improved inhibitory activity imparted by altering the hydrophobic substitution pattern at the bulky cap group is a valuable approach in the development of novel HDAC inhibitors.
    No preview · Article · Mar 2014 · ChemMedChem
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Effective delivery of therapeutic biomolecules across biomembranes is a challenging topic. A cationic cyclopeptide named TD-34 (ACSSKKSKHCG) was reported to improve insulin delivery across biomembranes effectively. Based on our previous work, we investigated the mechanism of TD-34 for enhancing insulin across Caco-2 cell monolayers. Transport studies of insulin, TD-34 and insulin accompanied with TD-34 were performed respectively using Caco-2 cell monolayers at different conditions. Transepithelial electrical resistance (TEER) value was monitored for 24 h immediately after the beginning of transport experiments. Moreover, the tight junction protein (Claudin-1) was localized by confocal immunofluorescence microscopy. Results showed the transport of insulin alone across biomembranes was attributable to multiple routes including passive diffusion. When TD-34 accompanied with or without insulin was treated on Caco-2 cell monolayers, TEER values decreased reversibly, and it was correlated with the reappearance of tight junction proteins by immunostaining assay. It was concluded that the cationic cyclopeptide (TD-34) had the potential to enhance paracellular delivery of insulin across Caco-2 cell monolayers by loosening tight junction reversibly.
    Full-text · Article · Aug 2013 · Biological & Pharmaceutical Bulletin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Poor permeability of stratum corneum limits the transportation of insulin across the skin. Transdermal peptide has exhibited enhancement activity on insulin transdermal delivery. Series cationic cyclopeptides based on the sequence of TD-1 (ACSSSPSKHCG) were designed by partial arginine or lysine scan method. Among these peptides, TD-34 (ACSSKKSKHCG) with bis-substituted lysine in N-5 and N-6 showed the best transdermal enhancement activity, the blood glucose level lower to about 26% of initial after administrating 2.1 IU insulin with 0.5 µmol TD-34 in 100 µL saline for 8h to diabetic rats in vivo. In addition, the transmembrane permeability in Caco-2 cell monolayers (BL→AP) exhibited preferable correlation with percutaneous absorption of insulin (R2 = 0.73). It can be concluded that appropriate content and position of cationic group in cyclopeptides may improve percutaneous absorption and transmembrane ability of insulin, and Caco-2 cell monolayers (BL→AP) might be applied to predict the percutaneous absorption of insulin chaperoned by a transdermal peptide in vivo.
    No preview · Article · Feb 2013 · Molecular Pharmaceutics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histone deacetylase inhibitors (HDACIs) are a promising class of anticancer agents. To examine whether a slight change in the recognition domain could alter their inhibitory activity, we synthesized a series of cyclo(-L-Am7(S2Py)-Aib-L-Phe(n-Me)-D-Pro)derivatives and evaluated their HDAC inhibitory and anticancer activities. The peptides exhibited potent HDAC inhibitory activity and inhibited three human cancer cell lines with IC₅₀ in the micromolar range. Docking and molecular dynamics simulation were conducted to explore the interaction mechanisms of class I and II HDACs with these inhibitors. It revealed that the zinc ion in the active site coordinated five atoms of HDACs and the sulfur atom of the inhibitor. The metal binding domains of these compounds interacted with HDAC2, and the surface recognition domains of these compounds interacted with HDAC4 through hydrogen bonding. The hydrophobic interactions also provided favorable contributions to stabilize the complexes. The results obtained from this study would be helpful for us to design some novel cyclic tetrapeptides that may act as potent HDACIs.
    No preview · Article · Apr 2012 · Journal of Peptide Science
  • Dawei Huang · Xiaohui Li · Yingdong Wei · Zhilong Xiu
    [Show abstract] [Hide abstract]
    ABSTRACT: Histone deacetylases inhibitors (HDACIs) have become an attractive class of anticancer agents. In order to find some novel potent HDACIs, we designed and synthesized a series of l-2-benzyloxycarbonylamino-8-(2-pyridyl)-disulfidyloctanoic acid derivatives. All compounds exhibited potent HDAC-inhibitory activity, and two of them had similar potency to TSA. The introduction of 2-amino-4-phenylthiazole or 9-methyleneoxy-fluorenyl group at the surface recognize domain of these HDACIs could greatly increase their HDAC-inhibitory activity. Molecular modeling studies indicated that coordination of the zinc ion by these inhibitors, and formation of hydrogen bond and hydrophobic interaction between inhibitors and HDACs were essential for the HDAC-inhibitory activities of these inhibitors. Asp181, Asp269, Leu276 and Tyr308 in the active site of HDAC2 gave favorable contributions for binding with all compounds.
    No preview · Article · Mar 2012 · European Journal of Medicinal Chemistry
  • Jie Zhang · Xiaohui Li · Daijia Zhang · Zhilong Xiu
    [Show abstract] [Hide abstract]
    ABSTRACT: Spraying and spraying with an electrostatic field (SEF) were employed to prepare alginate microspheres for delivering proteins, especially for intestinal digestive enzymes and cytokines. The encapsulation efficiency (EE) of a model protein [bovine serum albumin (BSA)] at a pH value lower than the isoelectric point was 20% higher than that at a natural pH. Moreover, for the microspheres prepared by SEF, EE improved significantly with increasing electric voltage. The interactions between BSA and the alginate microspheres were identified with Fourier transform infrared spectroscopy. The release profiles in vitro showed a controlled and pH-responsive release manner for the encapsulated BSA. A first-order release equation was postulated and modified to describe the release kinetics with an obviously initial burst release related to the eroded porous matrix. The equation fit the release data well when the pH value and composition of the release media were changed. The analysis of the release kinetics indicated that the drug release rate was in an inverse ratio to the diameter of the microspheres. Increasing the gas flow rate or electric voltage decreased both the mean diameter and size distribution of the microspheres significantly and enhanced the release rate of loaded drugs from alginate microspheres. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis analysis revealed that BSA kept its structural integrity during the encapsulation and release process. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
    No preview · Article · Nov 2008 · Journal of Applied Polymer Science
  • Chunli Yan · Zhilong Xiu · Xiaohui Li · Shenmin Li · Ce Hao · Hu Teng
    [Show abstract] [Hide abstract]
    ABSTRACT: Histone deacetylases (HDACs) play an important role in gene transcription, and inhibitors of HDACs can induce cell differentiation and suppress cell proliferation in tumor cells. Histone deacetylase1 (HDAC1) binds suberanilohydroxamic acid (SAHA) and 7-phenyl-2, 4, 6-hepta-trienoyl hydroxamic acid (CG-1521) with moderately low affinity (DeltaG = -8.6 and -7.8 kcal mol(-1)). The structurally related (E)-2-(3-(3-(hydroxyamino)-3-oxoprop-1-enyl)phenyl)-N(1),N(3)-diphenylmalonamide (SK-683), a Trichostatin A (TSA)-like HDAC1 inhibitor, and TSA are bound to the HDAC1 with -12.3 and -10.3 kcal mol(-1) of DeltaG, higher binding free energies than SAHA and CG-1521. Histone deacetylase-like protein (HDLP), an HDAC homologue, shows a 35.2% sequence identity of HDLP and human HDAC1. Molecular dynamics simulation and the molecular mechanics/generalized-Born surface area (MM-GBSA) free energy calculations were applied to investigate the factors responsible for the relatively activity of these four inhibitors to HDLP. In addition, computational alanine scanning of the binding site residues was carried out to determine the contribution components from van der Waals, electrostatic interaction, nonpolar and polar energy of solvation as well as the effects of backbones and side-chains with the MM-GBSA method. MM-GBSA methods reproduced the experimental relative affinities of the four inhibitors in good agreement (R(2) = 0.996) between experimental and computed binding energies. The MM-GBSA calculations showed that, the number of hydrogen bonds formed between the HDLP and inhibitors, which varied in the system studied, and electrostatic interactions determined the magnitude of the free energies for HDLP-inhibitor interactions. The MM-GBSA calculations revealed that the binding of HDLP to these four hydroxamic acid inhibitors is mainly driven by van der Waals/nonpolar interactions. This study can be a guide for the optimization of HDAC inhibitors and future design of new therapeutic agents for the treatment of cancer.
    No preview · Article · Oct 2008 · Proteins Structure Function and Bioinformatics
  • Xiaoqing Liu · Zhilong Xiu · Xiaohui Li
    [Show abstract] [Hide abstract]
    ABSTRACT: Many classes of functional cyclic peptide molecules are determined by experimental techniques, but few similarities of cyclic peptides are detectable. We propose three numerical characterizations of conformations of cyclic peptides. By incorporating the information on atomic coordinates of cyclic peptides, the coordinates are transformed into a characteristic sequence. Then we calculate its center of gravity, the eigenvalues of its Euclidean and L/L matrices, and regard them as descriptors to numerically characterize the conformations of cyclic peptides. Finally, the method is tested by analyzing the similarities of cyclic peptides presented in Table 1.
    No preview · Article · Dec 2007 · Journal of Computational Chemistry
  • Chunli Yan · Zhilong Xiu · Xiaohui Li · Hu Teng · Ce Hao
    [Show abstract] [Hide abstract]
    ABSTRACT: The inclusion interaction between quercetin and β-cyclodextrin (β-CD) binding site has been investigated, based on PM3 and ONIOM2 methods. The obtained results clearly indicate that the orientation in which the B ring of the guest molecule located near the secondary hydroxyls of the β-CD cavity is preferred in the binding energy. Moreover, Analyses regarding the complex structures suggest that one hydrogen bond between 7-hydroxy group (OH) of quercetin and 6-OH of β-CD is formed. This hydrogen bond interaction plays an important role in the bound quercetin/β-CD complex.
    No preview · Article · Jul 2007 · Journal of Inclusion Phenomena
  • Jie Zhang · Xiaohui Li · Daijia Zhang · Zhilong Xiu
    [Show abstract] [Hide abstract]
    ABSTRACT: In order to produce functional microspheres with different ranges of sizes for various applications, the size of alginate droplets prepared by dropping and spraying was studied. It was shown that the mean diameter could be controlled by liquid flow velocity and applied voltage as operating parameters using a conventional dropping and an electrostatic dropping method, separately. The formation mechanism of alginate droplets could be categorized into two different modes: Dripping mode and jetting mode. By employing an effective force analysis, the diameters in each modes showed to be well agreed with the numerical simulation within 7% deviations. It was testified that the initial amount of surface charges had a high impact on droplet diameter and the liquid flow velocity played a more important role on mean diameter of alginate droplets by electrostatic dropping method in dripping mode than in jetting mode. Then, an empirical equation and a semi-empirical model were used to simulate the diameter of droplets obtained by spraying and spraying with electrostatic field (SEF) method, respectively. The decrease in diameter was more sensitive to the increase of gas flow rate than to the decrease of liquid flow rate, and the results of two models fitted well with experimental values. The simulations showed that SEF yielded a 20% lower on droplet diameter than simple spraying method.
    No preview · Article · Jul 2007 · Journal of Microencapsulation
  • Source
    Chunli Yan · Xiaohui Li · Zhilong Xiu · Ce Hao
    [Show abstract] [Hide abstract]
    ABSTRACT: The inclusion process involving β-cyclodextrin (β-CD) and quercetin has been investigated by using the PM3 quantum-mechanical semi-empirical method. In the β-CD quercetin inclusion complex, a large portion of the flavonoid skeleton is included in the β-CD cavity and the bond connected ring B with ring C is inclined to the molecular axis of β-CD. The orientation in which the B ring of the guest molecule located near the secondary hydroxyls of the β-CD cavity is preferred in energy. One intermolecular hydrogen bond is formed. The molecular modeling results are in agreement with the NMR observations and molecular dynamics (MD) simulations. The statistical thermodynamic calculations at 1 atm and 298.15 K by PM3 demonstrate that 1:1 quercetin/β-CD complex is favored by a negative enthalpy change.
    Full-text · Article · May 2006 · Journal of Molecular Structure THEOCHEM