A new anti-diabetic sesquiterpenoid from Acorus calamus

A new sesquiterpenoid,1β,5α-guaiane-4β,10α-diol-6-one(1),was isolated from 70%EtOH extract of the rhizomes of Acorus calamus.The structure was determined on spectroscopic methods,especially 2D NMR techniques.The absolute configuration of 1 was confirmed by TDDFT quantum chemical calculation of its ECD spectrum.Compound 1 showed promising anti-diabetic activity on a insulin-mediated glucose consumption model of HepG2 cells.     

Maltase-glucoamylase inhibition potency and cytotoxicity of pyrimidine-fused compounds: An in silico and in vitro approach

The prevalence of diabetes mellitus has been incremented in the current century and the need for novel therapeutic compounds to treat this disease has been significantly increased. One of the most promising approaches is to inhibit intestinal alpha glucosidases. Based on our previous studies, four pyrimidine-fused heterocycles (PFH) were selected as they revealed satisfactory inhibitory action against mammalian α-glucosidase. The interaction of these compounds with both active domains of human maltase-glucoamylase (MGAM) and their effect on human Caco-2 cell line were investigated. The docking assessments suggested that binding properties of these ligands were almost similar to that of acarbose by establishing hydrogen bonds especially with Tyr1251 and Arg526 in both C-terminal and N-terminal MGAM, respectively. Also, these compounds indicated a stronger affinity for C-terminal of MGAM. L2 and L4 made tightly complexes with both terminals of MGAM which in turn revealed the importance of introducing pyrimidine scaffold and its hinge compartment. The results of molecular dynamics simulation analyses confirmed the docking data and showed deep penetration of L2 and L4 into the active site of MGAM. Based on cell cytotoxicity assessments, no significant cell death induction was observed. Hence, these functional MGAM inhibitors might be considered as new potential therapeutic compounds in treatment of diabetes and its complications.     

Greener pastures in evaluating antidiabetic drug for a quinoxaline Derivative: Synthesis,Characterization, Molecular Docking,in vitro and HSA/DFT/XRD studies

In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-4,5-dihydro-1H-1,2,3-triazol-1-yl)-N-(p-tolyl)acetamide (MOQTA) was synthesized and characterized by XRD and various spectroscopic tools (IR, ¹H &¹³C NMR, ESI-MS). The geometric optimization of the molecule was calculated with Density Functional Theory (DFT) method by B3LYP with a 6–311++G(d,p) basis set. Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of the title compound were generated. Furthermore, Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented. The calculated MEP and HSA surface interactions were compared in terms of hydrogen bonds and π-π stacking interactions obtained by X-ray packing analyses. X-ray crystallographic structure analysis revealed that the N—HN, C—HO and C—HN intermolecular hydrogen bonds were in agreement with those obtained by HSA. Moreover, MOQTA was assessed for its in vitro anti-diabetic activity. Likewise, molecular docking analyses were conducted to examine the binding mode between MOQTA and the enzymes α-glucosidase and α-amylase. Finally, the physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.     

New dimensions in triazolo[4,3-a]pyrazine derivatives: The land of opportunity in organic and medicinal chemistry

Synthesis of novel and potent hit molecules have endless demand. The triazolo[4,3-a]pyrazine scaffold is used as an essential building block/scaffold in organic synthesis, which works as a key template for the development of various therapeutic agents. It displays a wide spectrum of potential biological activities that have been progressively studied in recent years on account of their versatile structure and the diverse derivatives that can be synthesized from it to ensure functional motifs. This review article gives an inclusive account of the synthetic utility of triazolo[4,3-a] pyrazine derivatives employed in the design and synthesis of different types of compounds containing various active heterocyclic rings with greater emphasis in recent literature.     

Estimation of Metformin Drug for the Diabetes Patients by Simple,Quick and Cheap Techniques within the Formation of Colored Charge Transfer Complexes

Metformin (Met) is a drug developed for the treatment of patients with type Ⅱ diabetes. Recently, Met estimation in pharmaceutical formulations and human fluids has gained a growing interest. To extend requisite data that can be used to assessment of Met quantitatively based on charge-transfer (CT) complexation, the present study describes the synthesis and characterization of CT complexes that formed between drug Met and the organic π-acceptors picric acid (PA), chloranilic acid (CLA), chloranil (CHL), 7,7’,8,8’-tetracyanoquinodimethane (TCNQ), and dichlorodicyanobenzoquinone (DDQ). The properties of the formed CT complexes were investigated by elemental, spectral (UV-visible, IR, and Raman spectroscopies), thermal (TG) and morphological (SEM) studies. IR results indicated that the complexation of Met with either PA or CLA acceptors occurs through proton transfer interaction, whereas its complexation with CHL, TCNQ, or DDQ acceptors occurs through n→π* interaction.     

C18-attached membrane funnel-based spray ionization mass spectrometry for quantification of anti-diabetic drug from human plasma

In this work, sorbent-attached membrane funnel-based spray ionization mass spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked in human plasma. C₁₈-attached membrane funnel was fabricated for in situ extraction and clean-up to alleviate matrix suppression effect in the ionization process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under optimal working conditions, good linearity (R² > 0.99) was obtained in the concentration range of 1–100 ng mL⁻¹. The method detection limit of target drugs spiked in the human plasma was around 0.30 ng mL⁻¹. Through the application of an isotope-labeled internal standard, the signal fluctuation caused by residual background matrices was largely alleviated and the precision of measurement (RSD) was below 15%. The recovery of repaglinide for 5, 25, and 100 ng mL⁻¹ of spiked human plasma matrixes ranged from 87% to 112%. The developed method was successfully applied to determine repaglinide in plasma volunteers who orally received a dose of drug association. Our results demonstrated that membrane funnel-based spray is a simple and sensitive method for rapid screening analysis of complex biological samples.     

分子印迹复合膜对降糖药的拉曼光谱快速检测

基于分子印迹技术的特异性识别特点, 以假模板盐酸胍和4-(2-氨乙基)苯磺酰胺制备了2种分子印迹复合膜, 用其对保健品中的二甲双胍、 苯乙双胍和格列本脲进行吸附后, 采用拉曼光谱法实现了保健品中降糖药的富集与快速检测. 考察了膜制备过程中纳米银的加入对拉曼光谱的增强作用, 以及吸附样品浓度等的影响. 实验结果表明, 盐酸胍分子印迹复合膜吸附5 mg/mL以上的二甲双胍或苯乙双胍后具有明显的拉曼响应, 4-(2-氨乙基)苯磺酰胺印迹膜吸附10 mg/mL格列本脲后具有明显的拉曼响应. 所建立的分子印迹复合膜结合拉曼光谱检测方法可用于多种实际样品的检测.     

Design,synthesis and evaluation of potent G-protein coupled receptor 40 agonists

GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22g and 23e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.     

液相色谱-电喷雾串联质谱法同时测定蜂胶保健品中的活性成分和降糖西药

采用超高效液相色谱-电喷雾串联四极杆质谱仪(UPLC-ESI-MS/MS)同时测定蜂胶保健品中14种活性成分和9种违禁降糖西药。蜂胶保健品样品用甲醇稀释,超声波提取,样品溶液经高速离心后过滤。使用ACQUITY UPLC C18反相柱(50 mm×2.1 mm,1.7μm);流动相为0.3%甲酸溶液和乙腈,在梯度条件下分析,目标分析物在多反应监测(MRM)模式下以保留时间和离子对(母离子和两个碎片离子)信息比较进行定性和定量分析。本方法的活性成分检出限(LOD)为0.7～42.0 mg/kg;定量限(LOQ)为2.2～140 mg/kg;活性成分的加标回收率为77.8%～113.6%;违禁降糖西药的LOD为0.1～0.9 mg/kg,LOQ为0.3～2.5 mg/kg;违禁降糖西药的平均回收率为79.3%～108.5%。本方法简便、有效、灵敏,为评价蜂胶保健品质量提供了新的检测方法。     

A new paradigm for protein design and biological self-assembly

Very few molecules with biological origins contain the element fluorine. Nature's inability to incorporate fluorine into biomolecules is related to the low concentration of free fluoride in sea and surface water. However, judicious introduction of fluorine into proteins, nucleic acids, lipids and carbohydrates has allowed mechanistic scrutiny of enzyme catalysis, control of protein oligomerization in membranes, clustered display of ligands on surfaces of living cells, and in increasing the protease stability of protein and peptide therapeutics.