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Chinmedomics: A Powerful Approach Integrating Metabolomics with Serum pharmacochemistry to Evaluate the Efficacy of Traditional Chinese Medicine

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Engineering 2019年第1期5卷 60-68页

作者： Ai-Hua Zhang Hui Sun Guang-Li Yan Ying Han Qi-Qi Zhao Xi-Jun Wang National Chinmedomics Research Center & Sino-America Chinmedomics Technology Collaboration Center & National TCM Key Laboratory of Serum pharmacochemistry & Laboratory of Metabolomics Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine Harbin 150040 China

Evaluation of the efficacy of traditional Chinese medicines (TCMs) is an important prerequisite for discovering effective substances, lead compounds, and quality markers (Q markers). At present, there is an urgent need to develop a biological language that can act as abridge for the scientific elaboration of the efficacy of TCMs, and to further highlight the significant value of TCM. Chinese medicinal syndromes and formulae are two essential parts of TCM that directly relate to its efficacy. Syndromes and formulae have been taken as the research objects. The serum pharmacochemistry of the TCM approach with metabolomics were integrated to establish an innovative chinmedomics strategy, which is able to explore syndrome biomarkers and evaluate TCM efficacy in order to discover effective substances from TCMs. A great deal of concrete work in chinmedomics has already performed to bridge the gap between Chinese and Western medicine, and to provide a powerful approach to enhance the scientific value of TCM theory and clinical practice. This article summarizes the application of chinmedomics in identifying the candidate biomarkers of a syndrome and revealing the efficacy of the related formula. We also highlight the discovery of lead compounds and Q markers from TCMs.

关键词： Chinmedomics Serum pharmacochemistry of TCM Efficacy Metabolomics Syndrome Biomarkers Quality markers

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Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

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Open Journal of Medicinal Chemistry 2020年第3期10卷 57-112页

作者： Ouattara Mahama Coulibaly Songuigama N’Guessan Deto Jean-Paul Department of Therapeutic Chemistry and Organic Chemistry UFR Pharmaceutical and Biological Sciences FHB University Abidjan C&#244 te d’Ivoire

Antibiotic macrolides are experiencing renewed interest in anti-infective therapy since the advent of ketolides. This therapeutic class was introduced in order to broaden the narrow antibacterial spectrum of macrolides and to cope with the emergence of germs resistant to Erythromycin A and its hemisynthetic derivatives or neomacrolides (Clarithromycin, Roxithromycin, Azithromycin, Dirithromycin). From a pharmacochemical point of view, ketolides were first of all obtained by operating chemical modulations on Erythromycin A to obtain the neomacrolides, then, by replacing the neutral sugar (L-cladinose) in C3 by a ketone function coupled with the creation of an oxazolidinone like heterocycle in C11 and C12 in place of the hydroxyls present in these positions (Telithromycin, Cethromycin, Solithromycin). These modulations have enabled the improvement of the chemical stability of ketolides in gastric acid medium and increase their affinity for the ribosomal target, hence the broadening of their spectrum of action towards Gram positive germs including strains resistant to other macrolides and to neomacrolides. Therefore, the objective of this systematic review is to report the various pharmacochemical aspects undertaken since 1952 in the macrolide series based on the structure of Erythromycin A. These aspects will focus on the pharmacomodulations that have led, year after year, to the optimization of stability, the improvement of the pharmacodynamic and pharmacokinetic profile and that have allowed the development of neomacrolides, ketolides and neoketolides, which are today essential in the management of severe bronchopulmonary infections.

关键词： pharmacochemistry Erythromycin Neomacrolide Ketolide Neoketolide Structure-Activity Relationships

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