Technetium(I) tricarbonyl complexes: potential precursors of the radiopharmaceuticals. Part II: phenethylbiguanide (phenformin)

Fuks, L.; Gniazdowska, Ewa; Koźmiński, Przemysław; Herdzik-Koniecko, Irena

doi:10.1007/s10967-011-1417-z

Cited by 4 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since metformin and its derivatives were shown to effectively bind minor/major groove of DNA in both intercalative and non-intercalative mode [108,109], they might enhance the accumulation of 99m Tc radionuclides in the vicinity of DNA. Tricarbonyl 99m Tc(I) complex 30 with phenformin was prepared in two steps starting from readily available Na 99m TcO 4 (Scheme 13) [110]. Complex 30 demonstrated high stability in the presence of histidine and cysteine and moderate stability in rat serum and might exhibit some potential as a radiotherapeutic agent; however, its interaction with DNA has not been studied [110].…”

Section: Group VII (Mn Tc Re)mentioning

confidence: 99%

“…Tricarbonyl 99m Tc(I) complex 30 with phenformin was prepared in two steps starting from readily available Na 99m TcO 4 (Scheme 13) [110]. Complex 30 demonstrated high stability in the presence of histidine and cysteine and moderate stability in rat serum and might exhibit some potential as a radiotherapeutic agent; however, its interaction with DNA has not been studied [110].…”

Section: Group VII (Mn Tc Re)mentioning

confidence: 99%

See 1 more Smart Citation

Biological Properties of Transition Metal Complexes with Metformin and Its Analogues

2022

View full text Add to dashboard Cite

Metformin is a widely prescribed medication for the treatment and management of type 2 diabetes. It belongs to a class of biguanides, which are characterized by a wide range of diverse biological properties, including anticancer, antimicrobial, antimalarial, cardioprotective and other activities. It is known that biguanides serve as excellent N-donor bidentate ligands and readily form complexes with virtually all transition metals. Recent evidence suggests that the mechanism of action of metformin and its analogues is linked to their metal-binding properties. These findings prompted us to summarize the existing data on the synthetic strategies and biological properties of various metal complexes with metformin and its analogues. We demonstrated that coordination of biologically active biguanides to various metal centers often resulted in an improved pharmacological profile, including reduced drug resistance as well as a wider spectrum of activity. In addition, coordination to the redox-active metal centers, such as Au(III), allowed for various activatable strategies, leading to the selective activation of the prodrugs and reduced off-target toxicity.

show abstract

Section: Group VII (Mn Tc Re)mentioning

confidence: 99%

Section: Group VII (Mn Tc Re)mentioning

confidence: 99%

Biological Properties of Transition Metal Complexes with Metformin and Its Analogues

2022

View full text Add to dashboard Cite

show abstract

“…The binding forces and “on–off” kinetics depend, in part, upon the identity of the particular metal in the hetero-complex. For example, the preformed 99m Technetium- phenformin complex is sufficiently stable to be used in radiopharmaceutical imaging after parenteral administration (Fuks et al 2011). Some of the non-biological metal species might be relevant to medicinal or other applications of protease inhibition, e.g.…”

Section: The Stabilities Of Various Drug-metal-protease Complexes Arementioning

confidence: 99%

“…Some of the non-biological metal species might be relevant to medicinal or other applications of protease inhibition, e.g. platinum, vanadium, chromium, iridium, paladium, nickel, technetium, lanthanum, cesium, yttrium, samarium, and others (Woo et al 1999; Patrinoiu et al 2003; Fuks et al 2011; Al-Saif and Refat 2013; Badea et al 2013; Beygzadeh et al 2013; Shahabadi and Heidari 2014; Refat et al 2015; Mahmoud et al 2016; Chen et al 2018; Mihalache et al 2018). Metal toxicity is an obvious concern.…”

Section: The Stabilities Of Various Drug-metal-protease Complexes Arementioning

confidence: 99%

Biguanide is a modifiable pharmacophore for recruitment of endogenous Zn2+ to inhibit cysteinyl cathepsins: review and implications

Lockwood

2019

Biometals

View full text Add to dashboard Cite

Excessive activities of cysteinyl cathepsins (CysCts) contribute to the progress of many diseases; however, therapeutic inhibition has been problematic. Zn 2 + is a natural inhibitor of proteases with CysHis dyads or CysHis(Xaa) triads. Biguanide forms bidentate metal complexes through the two imino nitrogens. Here, it is discussed that phenformin (phenylethyl biguanide) is a model for recruitment of endogenous Zn 2 + to inhibit CysHis/CysHis(X) peptidolysis. Phenformin is a Zn 2 + -interactive, anti-proteolytic agent in bioassay of living tissue. Benzoyl- l -arginine amide (BAA) is a classical substrate of papain-like proteases; the amide bond is scissile. In this review, the structures of BAA and the phenformin-Zn 2 + complex were compared in silico. Their chemistry and dimensions are discussed in light of the active sites of papain-like proteases. The phenyl moieties of both structures bind to the “S2” substrate-binding site that is typical of many proteases. When the phenyl moiety of BAA binds to S2, then the scissile amide bond is directed to the position of the thiolate-imidazolium ion pair, and is then hydrolyzed. However, when the phenyl moiety of phenformin binds to S2, then the coordinated Zn 2 + is directed to the identical position; and catalysis is inhibited. Phenformin stabilizes a “Zn 2 + sandwich” between the drug and protease active site. Hundreds of biguanide derivatives have been synthesized at the 1 and 5 nitrogen positions; many more are conceivable. Various substituent moieties can register with various arrays of substrate-binding sites so as to align coordinated Zn 2 + with catalytic partners of diverse proteases. Biguanide is identified here as a modifiable pharmacophore for synthesis of therapeutic CysCt inhibitors with a wide range of potencies and specificities. Graphical abstract Phenformin-Zn 2+ Complex

show abstract

Technetium(I) carbonyl complexes for nuclear medicine: Coordination-chemical aspect

Sidorenko

Miroslavov²,

Tyupina³

2023

Coordination Chemistry Reviews

View full text Add to dashboard Cite

Technetium(I) tricarbonyl complexes: potential precursors of the radiopharmaceuticals. Part II: phenethylbiguanide (phenformin)

Cited by 4 publications

References 27 publications

Biological Properties of Transition Metal Complexes with Metformin and Its Analogues

Biological Properties of Transition Metal Complexes with Metformin and Its Analogues

Biguanide is a modifiable pharmacophore for recruitment of endogenous Zn2+ to inhibit cysteinyl cathepsins: review and implications

Technetium(I) carbonyl complexes for nuclear medicine: Coordination-chemical aspect

Contact Info

Product

Resources

About