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Clinical Observation on Trigonella Foenum-graecum L.Total Saponins in Combination with sulfonylureas in the Treatment of Type 2 Diabetes Mellitus

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Chinese Journal of Integrative Medicine 2008年第1期14卷 56-60页

作者：卢芙蓉沈霖秦铀高兰李恒戴燚 Department of Integrated Chinese and Western Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan(430022)

Objective： To evaluate the efficacy and safety of trigonella foenurn-graecurn L. total saponins （TFGs） in combination with sulfonylureas （SU） in the treatment of patients with type 2 diabetes mellitus （T2DM） not well controlled by SU alone. Methods： Sixty-nine T2DM patients whose blood glucose levels were not well controlled by oral sulfonylureas hypoglycemic drug were randomly assigned to the treated group （46 cases） and the control group （23 cases）, and were given TFGs or placebo three times per day, 6 pills each time for 12 weeks, respectively. Meanwhile, the patients continued taking their original hypoglycemic drugs. The following indexes, including effects on traditional Chinese medicine （TGM） symptoms, fast blood glucose （FBG）, 2-h post-prandial blood glucose （2h PBG）, glycosylated hemoglobin （HbAlc）, clinical symptomatic quantitative scores （CSQS）, body mass index （BMI）, as well as hepatic and renal functions, were observed and compared before and after treatment. Results： The efficacy on TCM symptoms was obviously better in the treated group than that in the control group （P〈0.01）, and there were statistically remarkable decreases in aspect of FBG, 2h PBG, HbAlc and CSQS in the treated group as compared to those in the control group （P〈0.05 or P〈0.01）, while no significant difference was found in BMI, hepatic and renal functions between the two groups （P〉0.05）. Conclusion： The combined therapy of TFGs with sulfonylureas hypoglycemic drug could lower the blood glucose level and ameliorate clinical symptoms in the treatment of T2DM, and the therapy was relatively safe.

关键词： trigonella foenurn-graecurn L. type 2 diabetes mellitus sulfonylureas

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Study on the bioactivity changes of hydroxylated sulfonylureas derivatives: A possible metabolism

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Chinese Chemical Letters 2007年第2期18卷 205-208页

作者： Shu Rong Ban Cong Wei Niu Wen Bin Chen Zhi Hong Yu Si Wu Chen Wang Zhen Xi State-Key Laboratory of Elemento-Organic Chemistry Department of Chemical BiologyNankai UniversityTianjin 300071China School of Pharmaceutical Science Shanxi Medical UniversityTaiyuan 030001China

Some new sulfonylureas and their hydroxylation products had been synthesized from 2-amino-4-methylpyrimidine. Their bioactivities against E. coli AHAS II in vitro were tested and the results indicated that the hydroxylation decreased the inhibition activities of sulfonylureas significantly. Subsequently herbicidal tests against stem-growth of barnyard grass and root-growth of rape confirmed the above conclusion. The preliminary molecular docking studies were also carried out to investigate the binding modes of non-hydroxylated and hydroxylated sulfonylureas with AHAS.

关键词： sulfonylureas Metabolism Hydroxylation E. coli AHASII Molecular docking

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Anti-aging effects of chlorpropamide depend on mitochondrial complex-Ⅱ and the production of mitochondrial reactive oxygen species

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Acta Pharmaceutica Sinica B 2022年第2期12卷 665-677页

作者： Zhifan Mao Wenwen Liu Yunyuan Huang Tianyue Sun Keting Bao Jiali Feng Alexey Moskalev Zelan Hu Jian Li State Key Laboratory of Bioreactor Engineering Frontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignEast China University of Science and TechnologyShanghai 200237China Laboratory of Geroprotective and Radioprotective Technologies Institute of BiologyKomi Science CentreUral BranchRussian Academy of SciencesSyktyvkar 167982Russia Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan College of PharmacyDali UniversityDali 671000China Clinical Medicine Scientific and Technical Innovation Center Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200092China

sulfonylureas are widely used oral anti-diabetic drugs.However,its long-term usage effects on patients’lifespan remain controversial,with no reports of influence on animal longevity.Hence,the anti-aging effects of chlorpropamide along with glimepiride,glibenclamide,and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+(mito K-ATP)channels and mitochondrial complex II.Chlorpropamide delayed aging in Caenorhabditis elegans,human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice.In addition,the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms,which is consistent with the function of its reported targets,mito K-ATP channels.Increased levels of mitochondrial reactive oxygen species(mt ROS)were observed in chlorpropamide-treated worms.Moreover,the lifespan extension by chlorpropamide required complex II and increased mt ROS levels,indicating that chlorpropamide acts on complex II directly or indirectly via mito K-ATP to increase the production of mt ROS as a pro-longevity signal.This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C.elegans.

关键词： sulfonylureas Chlorpropamide Anti-aging Mitochondrial complexⅡ Mitochondrial reactive oxygen species ATP sensitive potassium channels Senescence Succinate dehydrogenase

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Design, synthesis and bioactivity of novel herbicides targeted ALS (Ⅶ): Quantitative structure-activity relationships of herbicidal sulfonylureas

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Chinese Journal of Chemistry 1999年第6期17卷 650-657,5页

作者：杨光富杨华铮 Institute of Organic Synthesis Central China Normal University Wuhan Hubei 430079 China Institute of Elemento-Organic Chemistry Nankai University Tianjin 300071 China

The quantitative relationship between the structures of 20 sulfonylureas and their herbicidal activities against rape was analyzed using physicochemical parameters and regression analysis. The results showed that the electronic properties of the molecules are the dominant factor to the activity and there is apparently an optimum electronic property (∑σ or pKa) for the molecules to fit the receptor. Combined with the previous QSAR results for herbicidal triazolopyrimidine-2-sulfonamides, we can conclude that the structure-activity relationships of these two sets of compounds are identical, which suggested that these two sets of compounds acted on the same target site.

关键词： ALS inhibitors QSAR sulfonylureas herbicides

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HNF1A mutation in a Thai patient with maturity-onset diabetes of the young: A case report

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World Journal of Diabetes 2019年第7期10卷 414-420页

作者： Nattachet Plengvidhya Watip Tangjittipokin Nipaporn Teerawattanapong Tassanee Narkdontri Pa-thai Yenchitsomanus Division of Endocrinology and Metabolism Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Siriraj Center of Research Excellence for Diabetes and Obesity Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Immunology Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Research Division Department of Research and DevelopmentFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Siriraj Center of Research Excellence for Molecular Medicine Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand

BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common form of monogenic diabetes.The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year.MODY 3 is caused by mutation of hepatocyte nuclear factor(HNF)1A genes and is the most common MODY subtype.Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea.In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued.CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old.The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance.Sanger sequencing of proband’s DNA identified mutation of HNF1A at codon 203 which changed amino acid from arginine to cysteine(R203C).This mutation was carried only by family members who have diabetes.The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide(20 mg/d).Insulin therapy was successfully discontinued.CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient.Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.

关键词： Oral sulfonylureas Maturity-onset diabetes of the young HNF1A Case report

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Synthesis and Characterization of Novel-4-Methyl-3-isoxazolidinone Derivatives

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Chemical Research in Chinese Universities 2006年第6期22卷 717-720页

作者： GAO Fei-fei ZHANG Guang-liang ZHENG Liang-yu LI Yao-xian ZHANG Suo-qin College of Chemistry Ministry of Education Jilin University Changchun 130021 P. R. China Key Lab for Molecular Enzymology and Engineering Ministry of Education Jilin University Changchun 130021 P. R. China

A novel type of aeetohydrexyacid synthase inhibitors, 4-methyl-3-isoxazolidinone derivatives of sulfonylurea, was designed and synthesized. The structures of these compounds were confirmed by using MS, NMR, and elemen... 详细信息

关键词： 4-Methyl-3-isoxazolidinone sulfonylureas Acetohydroxyacid synthase Herbicidal activity

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Sulfonylurea Glimepiride: A Proven Cost Effective, Safe and Reliable War Horse in Combating Hyperglycemia in Type 2 Diabetes

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Journal of Diabetes Mellitus 2015年第4期5卷 211-226页

作者： Udaya M. Kabadi Broadlawns Medical Center Des Moines Iowa Des Moines University Des Moines Iowa and University of Iowa Iowa City Iowa USA

Recently, a debate has been raised regarding the place and the role of sulfonylureas (SU) amongst the armamentarium of drugs available for treatment of hyperglycemia in subjects with type 2 diabetes mellitus. With the advent of new drugs, SUs are being relegated and denigrated by some authorities contrary to present recommendations by various organizations e.g. American Diabetes Association, European Association for the Study of Diabetes and International Diabetes Federation. In this article, the advantages of SUs over the new agents in terms of their well established and proven better efficacy as well as their short term and long term (over 50 years) safety based on extensive literature data are documented. Moreover, lower costs of SUs render them to be far more cost effective when compared to new agents and therefore make them affordable in many regions of the world. Additionally, SUs are probably the initial drugs of choice in lean subjects with prediabetes and type 2 diabetes because they are the most effective secretogogues and major pathophysiologic mechanism of altered glucose metabolism in lean subjects is the decline in insulin secretion and not rising insulin resistance. Furthermore, SUs are also the most cost effective 2nd line agents in obese subjects with type 2 diabetes on lapse of glycemic control while receiving metformin. Finally, with progression of the disorder, the most cost effective combination of 2 oral agents in conjunction with basal insulin remains to be metformin and SUs. Many studies have documented a significantly greater extra pancreatic effect of glimepiride in comparison to other SUs probably because of its unique property in enhancing insulin sensitivity in conjunction with its ability to stimulate both 1st and 2nd phase insulin secretion. These characteristics may contribute to its greater efficacy with lesser hypoglycemia when compared with other SUs. Lack of hypoglycemic effect of metabolites of glimepiride may also be responsible for lesser hypoglycaemia. Moreover, metabolism

关键词： Type 2 Diabetes sulfonylureas (SU)

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Antidiabetic treatment, stroke severity and outcome

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World Journal of Diabetes 2014年第2期5卷 84-88页

作者： Dimitra Magkou Konstantinos Tziomalos First Propedeutic Department of Internal Medicine Medical School Aristotle University of Thessaloniki AHEPA Hospital

Ischemic stroke is a leading cause of mortality and long-term disability worldwide. Given the detrimental effects of acute stroke, several neuroprotective agents have been evaluated in these patients. However, the benefits of the evaluated agents appear to be limited and none is currently recommended for clinical use. On the other hand, prior treatment with agents that are used for the primary and secondary prevention of stroke, including statins and antiplatelets, has been associated with better outcome in patients who experience an acute stroke. In contrast, there are limited data as to whether prior treatment with antidiabetic agents is beneficial in diabetic patients who suffer a stroke. In this context, the findings of a recent study that showed reduced stroke size following pretreatment with linagliptin, a dipeptidyl peptidase-4(DDP-4) inhibitor, compared with glimepiride, in both diabetic and non-diabetic mice, appear promising. Despite these preclinical findings suggesting neuroprotective effects of DPP-4 inhibitors in acute stroke, it is still unclear whether these actions will also be observed in humans. Of note, two recent large randomized, placebo-controlled studies did not show any effect of DPP-4 inhibitors on cardiovascular events, including stroke. Several other ongoing trials are evaluating the effects of DPP-4 inhibitors on cardiovascular morbidity and mortality. These studies also provide a major opportunity to assess whether patients treated with this class of antidiabetic agents will suffer from less severe strokes and whether their outcome after stroke will be more favorable.

关键词： Type 2 diabetes mellitus Stroke Dipeptidyl peptidase-4 inhibitors sulfonylureas Neuroprotection

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Rhodium(Ⅲ)-Catalyzed Intermolecular Unactivated Secondary C(sp3)-H Bond Amidation Assisted by 3,5-Dimethylpyrazole

Rhodium(Ⅲ)-Catalyzed Intermolecular Unactivated Secondary C...

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中国化学会·第十六届全国有机合成化学学术研讨会

作者：王衍伟 Hongxin Liu Bin Li Baiquan Wang 南开大学 State Key Laboratory of Elemento-Organic Chemistry College of ChemistryNankai University

Transition-metal-catalyzed amination of unactivated C(sp)-H bond has undergone a breakthrough in recent years. However,most of them focus on the primary C(sp)-H bond. Direct amination of intermolecular unactivated secondary C(sp)-H bond still remains highly challenge.Herein,Rh(Ⅲ)-catalyzed intermolecular unactivated secondary C(sp)-H bond amidation reactions via nitrene insertion assisted by 3,5-dimetlylpyrazole have been developed.This procedure tolerates a broad substrates scope including chain and cyclic N-alklyamides under mild conditions.Notably,the directing group 3,5-dimethylpyrazole of chain N-alkylamide substrates could be easily removed via cascade intermolecular amidation and intramolecular cyclization in one-pot affording the sulfonylureas by increasing the reaction temperature.

关键词： rhodium unactivated amidation sulfonylureas

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