Table of Content

29 February 2020, Volume 29 Issue 2

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Review

Pyridin-2(1H)-ones as HIV-1 NNRTIs: a combinatorial optimization strategy

Xixi Li, Qian Liu, Tao Sheng, Junyi Liu, Xiaowei Wang

2020, 29(2):  79-89.  DOI: 10.5246/jcps.2020.02.006

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With rapid spread of HIV (human immunodeficiency virus) on a global scale and increasingly severe drug-resistance of it, it is urgently necessary to develop novel effective anti-HIV drugs. Non-nucleoside reverse transcriptase inhibitor (NNRTIs) is one of the most significant antiretroviral drugs for fighting against HIV infection due to their various structures, unique mode of action, good efficacy and low toxicity. Pyridinone derivatives, a type of NNRTIs, have been reported to achieve remarkable development in the past few decades. In this review, we summarized current drug design and medicinal chemistry efforts toward the development of next-generation pyridinones as HIV-1 NNRTIs.



Original articles

Pharmacokinetics of different dosage of astragalus membranaceus of buyang huanwu decoction in rats with cerebral ischemic injury by microdialysis  combined with LC/MS

Shengxin Wang, Xiangli Yan, Haozhen Zheng, Jianye Yu, Aiming Yu, Xiao Shen, Lisheng Wang

2020, 29(2):  90-101.  DOI: 10.5246/jcps.2020.02.007

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To investigate the pharmacokinetics of effective components of Bu Yang Huang Wu Decoction (BYHWD) with different dosages of Astragalus (Yiqi groups and Huoxue groups ) applicating in rats with middle cerebral artery occlusion (MCAO). Replicating the animal model of cerebral ischemia-reperfusion in rats, establishing the liquid-mass spectrometry method for the determination of BYHWD and researching the pharmacokinetics of effective components of yiqi groups of BYHWD with different dosages of astragalus (3.09, 6.17, 12.34 g/Kg) and Huoxue goups (2.32 g/Kg) when applicated seperately in the rats suffering from cerebral ischemia reperfusion injury after femoral vein administration. The pharmacokinetics of formononetin and paeoniflorin in the different dosage groups of BYHWD met the one-compartment model, and the t_1/2 of formononetin and paeoniflorin in the low-dose Yiqi and Huoxue groups were (88.43±3.82, 69.18±0.11) min,  MRT were (138.56±4.83, 113.62±2.42) min, and AUC_0–t were (28 488.35±4800.32, 140 614.80±23 954.05) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the middle-dose Yiqi group and Huoxue group were (82.16±1.78, 67.08±3.69) min, and MRT were (127.95±2.70, 116.58±4.13), AUC_0–t were (48 619.25±6745.75, 159 026.00±15 003.33) ng/mL·min; The t_1/2 of formononetin and paeoniflorin in the high-dose Yiqi and Huoxue groups were (80.29±1.12, 69.69±0.87) min, and MRT was (128.79±1.46, 118.78±4.56) min, AUC_0–t were (109 942.90±13 101.83, 189 417.90±22 311.00) ng/mL·min. The concentration rate of formononetin t_{1/2 brain} was decreased with increase of Astragalus dose. However, no significant difference between these two variables was found during experiments. Furthermore, the experiments showed that the increasing dose of astragalus would affect the pharmacokinetic behavior of paeoniflorin in the Huoxue groups. More specifically, the result showed that paeoniflorin can be metabolized more slowly in the body when applicated in high dose of the jaundice administration groups . In this way, the effect of paeoniflorin can be lasted for longer time in the body and brain.



Comparison of dissolution profile characteristics of 11 berberine hydrochloride tablet brands in different dissolution media

Fei Yu, Wenli Zhou, Jiayi Kan, Can Peng

2020, 29(2):  102-112.  DOI: 10.5246/jcps.2020.02.008

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Berberine hydrochloride is commonly used to treat bacterial dysentery, gastroenteritis and other diseases. Many manufacturers are available on the market today, while the production process and formulation are quite different, which may directly affect the therapeutic effect of the drug. To this end, 11 different production producers of berberine hydrochloride tablets were collected according to the pharmacopeia berberine hydrochloride dissolution method (basket method). In addition, the dissolution process was carried out in four elution media with different pH, and the difference was similar (f₂). Factors were calculated to evaluate in vitro dissolution requirements, and in vitro dissolution of different manufacturers of berberine hydrochloride tablets was determined by high performance liquid chromatography (HPLC). The method was verified by linearity, precision, stability and robustness. Based on the f₂ value, there was a significant difference in the dissolution behavior of the formulations of most berberine hydrochloride tablet brands. This research provided the basis for further in-depth research in the later period. Although the drug specifications (0.1 g) were the same, the dissolution curve was different. This phenomenon may be attributed to the fact that the excipients and crystal form of the tablets affected the release and dissolution of the tablets in vitro.



The granule characteristics of yam, sweet potato and tapioca starches determined by gravitational field-flow fractionation

Yue Zou, Yang Li, Nanyin Han

2020, 29(2):  113-122.  DOI: 10.5246/jcps.2020.02.009

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To study the characteristics of tuber starchgranules, firstly, three kinds of common tuber starches were separated and characterized by gravitational field-flow fractionation (GrFFF) instrument, and the ratios of large and small starch granules A/B were calculated. Then, the liquid of peak A and peak B was collected and observed by scanning electron microscope (SEM) to verify the separation result of GrFFF. Secondly, the particle size distribution and crystal characteristics were characterized by particle size analyser, X-ray diffraction (X-ray) and fourier transform infrared spectroscopy (FT-IR). Three kinds of tuber starches all had the bimodal distribution in GrFFF. Peak A contained large particles, and peak B contained small particles. For yam starch, the ratio of starch granules A/B was much higher than 1; for sweet potato starch, the ratio was approximately equal to 1; for tapioca starch, the ratio was much lower than 1. Moreover, the starch granules of sweet potato and tapioca were both A-type crystallinity, while yam starch granules were C-type crystallinity. GrFFF could be used to characterize and separate large and small granules of tuber starches and estimate the ratio of starch granules A/B. Yam starch was suitable for the development of slowly digestible starch (one kind of functional food), which could delay the occurrence of metabolic syndrome, diabetes and cardiovascular diseases. Tapioca starch was suitable for plant capsules, which were safer than gelatin capsule and could prevent the “poison capsule” incident from happening.



Synthesis and anticancer evaluation of N-benzoyl-N'-phenyltiourea derivatives against human breast cancer cells (T47D)

Dini Kesuma, Siswandono, Bambang Tri Purwanto, Marcellino Rudyanto

2020, 29(2):  123-129.  DOI: 10.5246/jcps.2020.02.010

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New anti-breast cancer compounds have been found and may prove to have stronger activity. To predict the activities of N-benzoyl-N'-phenylthiourea (BPTU) derivatives, namely N-(3-chloro)benzoyl-N'-phenylthiourea (3-Cl-BPTU) and N-(3,4-dichloro)benzoyl-N'-phenylthiourea (3,4-2Cl-BPTU) with Sirtuin-1 receptor (PDB code: 4I5I), molecular docking was conducted at the beginning of this study. The compounds were then synthesized from benzoyl chloride derivatives and N-phenylthiourea. Molecular structure was confirmed using  FTIR, ¹H NMR, ¹³C NMR and Mass Spectra, while the anticancer activity was tested in vitro against human breast cancer cells (T47D) using MTT assay. The results indicated that the anti-cancer activities of the test compounds were better than those of the hydroxyurea as the reference compound, evidenced by the Rerank Score (RS). Furthermore, cytotoxic effect of 3-Cl-BPTU (IC₅₀: 0.43 mM) and 3,4-dichloro-BPTU (IC₅₀: 0.85 mM) showed better result compared with hydroxyurea (IC₅₀: 4.58 mM). Therefore, we concluded that these compounds could possess termendous potential as the candidate for a new anticancer drug.   



Construction and open access management of large-scale instrument platform

Shuxiang Song

2020, 29(2):  130-138.  DOI: 10.5246/jcps.2020.02.011

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Due to the new situation of continuous expansion of scientific and technological resources in universities and the urgent demand for hardware resources for science and technology innovation, it is imperative to strengthen the construction of large-scale instrument service platforms and open access management. It is not only the requirements for the development of instrument service platforms, but also the resources for science and technology of society. In the present paper, we first summarized the current equipment management, open access and major experience, then raised the problems in the construction and management process on the basis of the large instrument platform construction and open access management regulations, and finally proposed countermeasures for these problems: increasing funding input, streamlining the management system, improving the performance evaluation mechanism, and strengthening the management and operation team construction, etc. Collectively, this paper provided reference and enlightenment for the construction and open access management of similar large-scale instrument platforms.



Drug administration and clinical pharmacy column

Effects of drug purchasing under joint price caps policy in Fujian Province, China

Ruojing Zhou, Bin Jiang

2020, 29(2):  139-152.  DOI: 10.5246/jcps.2020.02.012

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To evaluate the long-term effect of Drug Purchasing under Joint Price Caps Policy in Fujian Province on price, prescription volume, medical insurance expense and patient’s burden, a total of 59 968 reimbursement records, during the period of 2012.1–2018.8, were processed into monthly data and analyzed through interrupted time series (ITS) regression models. The ITS analysis showed that after the implementation of the policy, (1) the price of competitive drugs was significantly increased by 128.9% (P<0.01), while the price of non-competitive drugs was significantly decreased by 18.9% (P<0.01). (2) The prescription volume of sample drugs was decreased by 32.3% (P<0.01), and that of competitive drugs was decreased by 45.9% (P<0.01), while that of non-competitive drugs was increased by 19.1% (P<0.01). (3) There was no significant change in the monthly medical insurance expense per capita of sample drugs. (4) There was no significant effect on the overall patient’s burden, while the out-of-pocket payment per capita of competitive drugs was increased by 81.4% (P<0.01).