Water-Soluble Nystatin and Derivative.

Fungal infections are increasingly causing more morbidity and mortality, especially for immunocompromised people. In recent years, there is growing evidence that new medicine-resistant fungal strains are posing added challenges in the clinic. Nystatin is a known antifungal from the polyene family.

Novel crown-ether-methylenediphosphonotetrathioate hybrids as Zn(II) chelators.

Hybrids of methylenediphosphonotetrathioate and crown-ether (MDPT-CE) were synthesized forming 7-,8-,9-,10- and 13-membered rings. Both 7- and 13-membered ring-containing compounds were found to be highly stable to air-oxidation for at least four weeks. These hybrids bind Zn(II) by both MDPT and CE moieties, forming a 2 : 1 L : Zn(II) complex.

Novel Cu(I)-selective chelators based on a bis(phosphorothioyl)amide scaffold.

Bis(dialkyl/aryl-phosphorothioyl)amide (BPA) derivatives are versatile ligands known by their high metal-ion affinity and selectivity. Here, we synthesized related chelators based on bis(1,3,2-dithia/dioxaphospholane-2-sulfide)amide (BTPA/BOPA) scaffolds targeting the chelation of soft metal ions. Crystal structures of BTPA compounds 6 (N(-)R3NH(+)) and 8 (NEt) revealed a gauche geometry, while BOPA compound 7 (N(-)R3NH(+)) exhibited an anti-geometry.

Nucleoside-(5'→P) methylenebisphosphonodithioate analogues: synthesis and chemical properties.

Nucleoside-(5'→P) methylenebisphosphonodithioate analogues are bioisosteres of natural nucleotides. The potential therapeutic applications of these analogues are limited by their relative instability. With a view toward improving their chemical and metabolic stability as well as their affinity toward zinc ions, we developed a novel nucleotide scaffold, nucleoside-5'-tetrathiobisphosphonate.

Methylenediphosphonotetrathioate: synthesis, characterization, and chemical properties.

Metal chelators are potential therapeutic agents for treating diseases such as Wilson's and Alzheimer's where the pathology involves an excess of metal-ions (Cu(II) and Zn(II)/Cu(II)/Fe(II/III), respectively). In addition to the high affinity of the metal-ion to the chelators, metal selectivity of the chelators is essential to achieve the therapeutic goal, that is, the successful removal of excess of harmful metal-ions in a physiological extracellular medium rich in alkali and alkali earth metal-ions. For this purpose, we synthesized a novel chelator, methylenediphosphonotetrathioate (MDPT) which is the tetrathio analogue of methylenediphosphonic acid (MDP).

O,O'-Diester methylenediphosphonotetrathioate: synthesis, characterization, and potential applications.

A new transformation of methylene-bis(phosphonic dichloride) into tetrathiobisphosphonate derivatives is reported. The reaction of methylene-bis(phosphonic dichloride) with 1,2-ethanedithiol in bromoform in the presence of AlCl(3) formed methylene-bis(1,3,2-dithiaphospholane-2-sulfide), which gave rise to O,O'-diester-methylenediphosphonotetrathioate analogues 1a-k upon reaction with phenols and alkyl alcohols in the presence of DBU. Reaction mechanisms are proposed, and all products were characterized by (31)P, (13)C, and (1)H NMR.

Nucleoside-5'-phosphorothioate analogues are biocompatible antioxidants dissolving efficiently amyloid beta-metal ion aggregates.

Amyloid beta (Aβ) peptide is known to precipitate and form aggregates with zinc and copper ions in vitro and, in vivo in Alzheimer's disease (AD) patients. Metal-ion-chelation was suggested as therapy for the metal-ion-induced Aβ aggregation, metal-ion overload, and oxidative stress. In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we tested a series of nucleoside 5'-phosphorothioate derivatives as re-solubilization agents of Cu(+)/Cu(2+)/Zn(2+)-induced Aβ-aggregates, and inhibitors of Fenton reaction in Cu(+) or Fe(2+)/H(2)O(2) system.