Yao Xiao

Publications (3)7.91 Total impact

• Article: An integrated drug-likeness study for bicyclic privileged structures: from physicochemical properties to in vitro ADME properties.

  Chunyan Han, Jinlan Zhang, Mingyue Zheng, Yao Xiao, Yan Li, Gang Liu
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  ABSTRACT: The concept of drug-likeness has been widely applied in combinatorial chemistry as an approach to reduce attrition in drug discovery and development. Meanwhile, bicyclic privileged structures with versatile binding properties have emerged as ideal source of core scaffolds for the design and synthesis of combinatorial libraries. For the purpose of better assisting the design of bicyclic privileged structure-based combinatorial libraries, we conducted an integrated drug-likeness study on compounds of these scaffolds. Distributions of physicochemical properties (PCPs) were analyzed and in silico prediction models were built. Our results showed that there exist much difference between the drug-like ranges (DLRs) of bicyclic privileged structures and that of others, which have significant impact on compound selection. The DLRs for bicyclic privileged structures were defined as 260 ≤ MW ≤ 524; 0.9 ≤ ALogP ≤ 5.4; 2 ≤ Hacc ≤ 8; Hdon ≤ 3; 21.0 ≤ PSA ≤ 128.6; 6.3 ≤ FPSA ≤ 34.2; 1 ≤ RotB ≤ 10; 2 ≤ Nr ≤ 5; 1 ≤ Nc ≤ 7; SA ≤ 4. Two accurate and easy to understand in silico prediction models, Caco-2 permeability model and metabolic stability classification model, had been built to guide drug candidate optimization. In these models, hydrogen-bond donor and rotatable bond showed major impact on the permeability of compounds, while lipophilicity, flexibility, degree of branching and the existence of some functional groups determined the fate of a drug in metabolic process. Suggestions on structural modification toward higher permeability and metabolic stability were given according to the in silico models.
  Molecular Diversity 05/2011; 15(4):857-76. · 3.15 Impact Factor
• Article: Identification of active compounds and their metabolites by high-performance liquid chromatography/electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry from Xiao-xu-ming decoction (XXMD).

  Yilin Wang, Chunguang Ding, Kehe Du, Yao Xiao, Caisheng Wu, Jinlan Zhang, Hailin Qin, Guanhua Du
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  ABSTRACT: Xiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100,000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD.
  Rapid Communications in Mass Spectrometry 07/2009; 23(17):2724-32. · 2.79 Impact Factor
• Article: LC-MS determination and pharmacokinetic studies of paeonol in rat plasma after administration of different compatibility of Su-Xiao-Xin-Tong prescriptions.

  Yao Xiao, Ying-hao Zhang, Yu-xin Sheng, Jin-lan Zhang
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  ABSTRACT: A rapid and specific liquid chromatographic/electrospray ionization mass spectrometric (LC/ESI-MS) method has been developed and validated for the identification and quantification of paeonol in rat plasma. Paeonol and internal standard were isolated from plasma samples by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Zorbax-SB C18 column (100x2.1 mm, 3.5 microm). The mobile phase consisted of acetonitrile and 0.1% aqueous formic acid (64:36) was delivered at a flow rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring mode via electrospray ionization source. Linearity was established for the range of concentrations 0.0525-15.8 microg/mL with a coefficient correlation (r) of 0.9995. The intra- and inter-day precision (RSD%) was lower than 9.34% and accuracy ranged from 93.7 to 102.3%. The lower limit of quantification was 0.0525 microg/mL. The proposed method was used to determine the concentration of paeonol for pharmacokinetic studies. The pharmacokinetics of different compatibility prescriptions of Su-Xiao-Xin-Tong were studied and compared.
  Biomedical Chromatography 06/2008; 22(5):527-34. · 1.97 Impact Factor