Research progresses on the main active components in Ningxia Sophora alopecuroides and the therapeutic activities for liver diseases / 药学实践杂志

Sophora alopecuroides, a plant of the family Leguminosae, is one of the Daodi herbs in Ningxia. The active constituents of Sophora alopecuroides are abundant and complex, including alkaloids, flavonoids, volatile oils, steroids, polysaccharides, fatty acids and so on. In recent decades, a great number of domestic and overseas studies have been carried out on Sophora alopecuroides alkaloids, which have anti-hepatitis, anti-liver fibrosis, anti-cirrhosis, anti-liver failure and anti-liver cancer and other pharmacological effects. Clinically, Matrine-related drugs are used to treat hepatitis B virus infection and other diseases. This review aims to summarize the main active ingredients of Sophora alopecuroides, mainly focusing on the research progress in their treatment activities for liver diseases.

Cytotoxicity study on FC58, an indole-chalcone, against multi-drug resistant leukemia cells / 药学实践杂志

Objective To synthesize and investigate cytotoxicity of an indole-chalcone derivative FC58. Methods The target compound was synthesized through the Aldol condensation with 1-(3,4,5-trimethoxyphenyl)ethan-1-one and 1H-indole-3-carbaldehyde. The Cell Titer-Blue method was used to determine in vitro cytotoxicity. The cell cycle experiment was performed to analyze the action characteristics of FC58. Results FC58 exhibited high cytotoxicity against various leukemia cells and resulted in G2/M phase arrest. It showed stronger drug resistant index than traditional tubulin inhibitors such as paclitaxel, vinblastine and doxorubicin. Conclusion FC58 represents a promising lead compound for multi-drug resistant leukemia.

Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy

Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (

Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years

Human immunodeficiency virus (HIV) is the primary infectious agent of acquired immunodeficiency syndrome (AIDS), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the cornerstone of HIV treatment. In the last 20 years, our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs, including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), thio-dihydro-alkoxy-benzyl-oxopyrimidine (-DABO), diaryltriazine (DATA), diarylpyrimidine (DAPY) analogues, and their hybrid derivatives. Application of integrated modern medicinal strategies, including structure-based drug design, fragment-based optimization, scaffold/fragment hopping, molecular/fragment hybridization, and bioisosterism, led to the development of several highly potent analogues for further evaluations. In this paper, we review the development of NNRTIs in the last two decades using the above optimization strategies, including their structure-activity relationships, molecular modeling, and their binding modes with HIV-1 reverse transcriptase (RT). Future directions and perspectives on the design and associated challenges are also discussed.

Research progress on small molecule inhibitors of coronaviruses / 药学实践杂志

Coronavirus infection seriously threatens human health. There is no specific medication or vaccine so far. In recent years, domestic and foreign researchers have developed a variety of small-molecule inhibitors against the ligand S protein, RdRp, PLpro and 3CLpro of three highly pathogenic coronavirus, SARS-CoV，MERS-CoV，SARS-CoV-2. This article reviews the characteristics of these coronaviruses, action targets, small molecule inhibitors, and structure-activity relationships.

Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

Methodology of drug screening and target identification for new necroptosis inhibitors / 药物分析学报

Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Thus, the study on the molecular mechanism of necroptosis and its effective inhibitors has been an attractive field for researchers. Herein, we introduce the molecular mechanism of necroptosis and focus on the literature about necroptosis drug screening in recent years. In addition, the identification of the critical drug targets of the necroptosis is also discussed.

Recent research progress on anti-microtubule agents targeting multi-drug resistant cancers / 药学实践杂志

In 2015, more than 8 million people died from various kinds of cancers all over the world.Although traditional chemotherapeutic drugs are widely used in clinic, more than 50％ of cancers are significantly resistant to traditional chemotherapeutic drugs.Tubulin targeting agents have been confirmed to be effective anti-cancer drugs in clinic.However, some anti-microtubule agents developed resistance after long-term use, such as paclitaxel and vinblastine.In recent years, it is reported that tubulin modulators targeting on the colchicine-binding site are extremely effective against multi-drug resistant cancer cells.In this article, different anti-microtubule agents targeting multi-drug resistant cancers are reviewed.

Research progress on the chemicals with cancer stem cell growth inhibitory activity / 中国生化药物杂志

Cancer stem cells play a crucial role in tumors'invasion, metastasis, recurrence and drug resistance.Investigation on the chemicals with tumor stem cell growth inhibitory activity has been greatly highlighted in the field of anti-tumor drug discovery.This paper briefly reviews the recent progress of chemical investigations on substances with tumor stem cell growth inhibitory activity , aiming to give readers a reference on anti-tumor drug discovery.

Study on chemical constitunts of sponge Agelas mauritiana from the South China Sea / 药学实践杂志

Objective To investigate the chemical constituents of marine sponge A gelas mauritiana collected from the South China Sea .Methods The n-butanol extract of marine sponge A gelas mauritiana was separated and purified by repeated column chromatography on silica gel ,Sephadex LH-20 ,and reversed-phase high-performance liquid chromatography (RP-HPLC) .The chemical structures of those obtained compounds were determined on the basis of spectroscopic analysis and com-parison with reported data .The tumor cell growth inhibitory activity of these compounds towards human lung carcinoma cells A549 was tested .Results Eight compounds were isolated ,including agelasine A (1) ,agelasine B (2) ,epi-agelasine C (3) , (-)agelasine D (4) ,agelasine E (5) ,agelasine F (6) ,(-)ageloxime D (7) and aurantiamide acetate (8) .These compounds dis-played different level of tumor cell growth inhibitory activity towards cell A 549 in vitro .Compounds 1-3 showed significant ac-tivity towards cell A549 ,being similar to that of the positive control of adriamycin .Conclusion Compounds 1 ,2 ,4 ,5 ,6 ,8 were isolated for the first time from the sponge A gelas mauritiana .Cell A549 was selected for the first time for the activity evalua-tion of compounds 1~7 .Significant inhibition activity of compounds 2、3 may hold as a basis for further research .