657-24-9Relevant academic research and scientific papers
A ternary tetracoordinated PdII complex with metformin and dipicolinate: Synthesis, characterization and crystal structure
Moghimi,Khavassi,Dashtestani,Kordestani,Ekram Jafari,Maddah,Moosavi
, p. 38 - 41 (2011)
A proton transfer compound L, (MetH)2(dipic), (dipicH 2 = 2,6-pyridinedicarboxylic acid and Met = Metformin (N,N-dimethylebiguanidine), was synthesized and characterized by IR, 1H and 13C NMR spectroscopy. The reaction of L with PdCl2 in water results in the formation of novel tetracoordinated PdII complex [Pd(dipic)(Met)]·2H2O indicating the participation of both dipic2- and Met as chelating ligands. This complex was characterized by single crystal X-ray analysis. The crystal system is monoclinic with space group P21/c. The unit cell dimensions for PdII complex 1 is a = 8.8619(14) , b = 9.5072(9) , c = 19.153(3) .
Novel halogenated sulfonamide biguanides with anti-coagulation properties
Huttunen, Kristiina M.,Markowicz-Piasecka, Magdalena,Sikora, Joanna,Zajda, Agnieszka
, (2019)
Apart from its hypoglycaemic properties, metformin also offers beneficial effects for the cardiovascular system resulting in significant reduction of diabetes-related death, and all-cause mortality. The aim of this study was to synthesize nine new benzenesulfonamide derivatives of metformin with a halogen substituent, and estimate their influence on selected parameters of plasma and vascular hemostasis. The study describes the synthesis of nine benzenesulfonamide biguanides with o-, m-, and p- chloro-, bromo-, and fluoro substituents. All orto- derivatives (chloro- (1), bromo- (4), and fluoro- (7)) significantly prolong prothrombin time (PT) and partially activated thromboplastin time (APTT). In addition compounds 4 and 7 slow the process of fibrin polymerization, and contribute to increased TT. Multiparametric CL-test revealed that compounds 1, 4, 7 and p-fluorobenzenesulfonamide (9) significantly prolong the onset of clot formation, decrease initial clot formation velocity, and maximum clotting. Analysis of human endothelial cell (HUVECs) and human aortal smooth muscle cell (AoSMCs) viability over the entire tested concentration range (0.001–3.0 μmol/mL) indicated that the examined compounds can undergo further tests up to 1.5 μmol/mL concentration without decreasing cellular viability. Furthermore, none of the synthesized compounds exert an unfavourable effect on erythrocyte integrity, and thus do not interact strongly with the lipid-protein bilayer. In summary, chemical modification of the metformin backbone into benzenesulfonamides containing halogen substituents at the o- position leads to the formation of potential agents with stronger anti-coagulant properties than the parent drug, metformin. Therefore, o-halogenated benzenesulfonamides can be regarded as an initial promising step in the development of novel biguanide-based compounds with anti-coagulant properties.
Convenient microwave-assisted synthesis of lipophilic sulfenamide prodrugs of metformin
Huttunen, Kristiina M.,Lepp?nen, Jukka,Laine, Krista,Veps?l?inen, Jouko,Rautio, Jarkko
, p. 624 - 628 (2013)
A convenient microwave-assisted synthesis of lipophilic sulfenamide prodrugs of antidiabetic agent, metformin, is reported in this study. These acyclic prodrugs were synthesized directly from selected disulfides with basic metformin and silver nitrate by a one-pot reaction under microwave irradiation. The prepared prodrugs had significantly increased lipophilicity, which resulted in excellent permeability of the octylthio prodrug of metformin across a Caco-2 cell monolayer. According to our preliminary in vivo studies, the octylthio prodrug was also absorbed mostly intact after oral administration in rats. In conclusion, this study shows that these types of more lipophilic sulfenamide prodrugs can be promising candidates to improve permeability and passive absorption of highly water-soluble metformin.
Solid state and solubility study of a potential anticancer drug-drug molecular salt of diclofenac and metformin
Feng, Wen-Quan,Wang, Ling-Yang,Gao, Jie,Zhao, Ming-Yu,Li, Yan-Tuan,Wu, Zhi-Yong,Yan, Cui-Wei
, (2021)
To improve the physicochemical properties of diclofenac (DFA) and exert its potential anti-tumor effect in combined pharmacotherapy of metformin (MET), a new drug-drug molecular salt of DFA and MET (DFA-MET) is formed and characterized. The single-crystal X-ray diffraction analysis shows that DFA-MET is a three-dimensional (3D) supramolecular structure constructed by different hydrogen-bonding interactions between DFA and MET with 1:1 stoichiometry by proton transfer reaction. In addition, Hirshfeld Surface analysis shows that both the hydrogen-bonding interactions and the Vander Waals maintain the 3D supramolecular structure of DFA-MET together. Compared with pure DFA and pure diclofenac sodium (NaDFA), the dissolving behavior and permeability of DFA-MET by forming drug-drug molecular salt in physiological pH environments are enhanced remarkably.
Two N,N-dimethylbiguanidium salts displaying double hydrogen bonds to the counter-ions
Lu, Li-Ping,Zhang, Hong-Mei,Feng, Si-Si,Zhu, Miao-Li
, (2004)
An investigation into the crystal structures of N,N-dimethylbiguanidium salts was made. Compound (I) in N,N-dimethylbiguanidium contained one N,N dimethylbiguanidium dictation, one oxalate anion and one water molecule. Compound (II) consisted of one N,N-d
Novel sulfonamide-based analogs of metformin exert promising anti-coagulant effects without compromising glucose-lowering activity
Markowicz-Piasecka, Magdalena,Sadkowska, Adrianna,Sikora, Joanna,Broncel, Marlena,Huttunen, Kristiina M.
, p. 1 - 28 (2020)
Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 μmol/L for comp. 6 at 0.3 μmol/mL versus 11.4 ± 0.7 μmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not a ect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.
Sulfonamide metformin derivatives induce mitochondrial-associated apoptosis and cell cycle arrest in breast cancer cells
Huttunen, Johanna,Huttunen, Kristiina M.,Markowicz-Piasecka, Magdalena,Sikora, Joanna,Zajda, Agnieszka
, (2021/12/31)
Metformin, an oral anti-diabetic drug, has attracted scientific attention due to its anti-cancer effects. This biguanide exerts preventive effects against cancer, and interferes with cancer-promoting signaling pathways at the cellular level. However, the direct cytotoxic or anti-proliferative effect of the drug is observed at very high concentrations, often exceeding 5–10 mM. This paper presents the synthesis of eight novel sulfonamide-based biguanides with improved cellular uptake in two breast cancer cell lines (MCF-7 and MDA-MB-231), and evaluates their effects on cancer cell growth. The synthesized sulfonamide-based analogues of metformin (1–5) were efficiently taken up in MCF-7 and MDA-MB-231 cells, and were characterized by stronger cytotoxic properties than those of metformin. Generally, compounds were more effective in MCF-7 than in MDA-MB-231. Compound 2, with an n-octyl chain, was the most active molecule with IC50 = 114.0 μmol/L in MCF-7 cells. The cytotoxicity of compound 2 partially results from its ability to induce early and late apoptosis. Increased intracellular reactive oxygen species (ROS) production and reduced mitochondrial membrane potential suggest that compound 2 promotes mitochondrial dysfunction and activates the mitochondrial-associated apoptosis-signaling pathway. In addition, compound 2 was also found to arrest cell cycle in the G0/G1 and G2/M phase and significantly inhibit cancer cell migration. In conclusion, this study supports the hypothesis that improved transporter-mediated cellular uptake of potential drug molecule is accompanied by its increased cytotoxicity. Therefore, compound 2 is a very good example of how chemical modification of a biguanide scaffold can affect its biological properties and improve anti-neoplastic potential.
5-substituted 2,4-thiazolidinediones (thiohydantoins), pseudothiohydantoins, and propseudothiohydantoins for use as antiviral agents
-
Page/Page column 13-14, (2020/06/03)
The present invention concerns the synthesis and use of formulations of 5-substituted 2, 4-thiazolidinediones, pseudothiohydantoins, and propseudothiohydantoins and 2, 4-thiazolidinediones metforminate salts for topical and systemic treatments of infections caused by herpes simplex viruses and varicella zoster viruses.
MODIFICATIONS OF THERAPEUTIC AGENTS FOR ENHANCED DELIVERY TO TARGET SITES
-
Paragraph 0475; 0476, (2018/02/28)
Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.
RAPAMYCIN ANALOGS AND USES THEREOF
-
Paragraph 00163; 00168, (2017/03/28)
The present invention provides compounds, compositions thereof, and methods of using the same.
