63075-66-1Relevant articles and documents
Metal ion-binding properties of 9-(4-phosphonobutyl)adenine (dPMEA), a sister compound of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), and quantification of the equilibria involving four Cu(PMEA) isomers
Gomez-Coca, Raquel B.,Kapinos, Larisa E.,Holy, Antonin,Vilaplana, Rosario A.,Gonzalez-Vilchez, Francisco,Sigel, Helmut
, p. 2077 - 2084 (2000)
The acidity constants of the threefold protonated acyclic 9-(4-phosphonobutyl)adenine, H3(dPMEA)+, as well as the stability constants of the M(H;dPMEA)+ and M(dPMEA) complexes with the metal ions M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+, have been determined by potentiometric pH titrations, in aqueous solution at I= 0.1 M (NaNO3) and 25 °C. Application of previously determined straight-line plots of log KM(R-PO3)M versus PKH(R-PO3)H for simple phosph(on)ate ligands, R-PO32-, where R represents a residue without an affinity for metal ions, proves that the primary binding site of dPMEA2- is the phosphonate group with all the metal ions studied; in fact, in most instances the stability is solely determined by the basicity of the phosphonate residue. Only for the Ni(dPMEA), Cu(dPMEA) and Cd(dPMEA) systems a stability increase due to macrochelate formation with the adenine residue occurs; the formation degrees are 21 ± 15%, 31 ± 14% and 29 ± 18%, respectively. In these three instances the additional interaction of the phosphonate-coordinated M2+ occurs most probably with N7; hence, dPMEA2- is more similar in its metal ion-binding properties to the parent nucleotide adenosine 5′-monophosphate (AMP2-) than to the antivirally active and structurally more related dianion of 9-[2-(phosphonomethoxy)ethyl]-adenine (PMEA2-). This result agrees with the observation that replacement of the ether O atom in PMEA by a CH2 unit leads to a compound, i.e. dPMEA, devoid of any biological activity. In addition, use is made of the stability enhancement obtained for the Cu(dPMEA) system due to macrochelate formation to analyze the equilibria regarding the four isomeric complex species possibly formed in the Cu(PMEA) system. It is shown that a macrochelated isomer involving N7 of the adenine residue occurs with Cu(PMEA) only in trace amounts; the important isomers in this system involve the ether oxygen (formation degree ca. 34%) and also N3 of the adenine moiety (ca. 41%). The Royal Society of Chemistry 2000.
Synthesis and biological activity investigation of azole and quinone hybridized phosphonates
Subedi, Yagya Prasad,Alfindee, Madher N.,Shrestha, Jaya P.,Becker, Greg,Grilley, Michelle,Takemoto, Jon Y.,Chang, Cheng-Wei Tom
supporting information, p. 3034 - 3037 (2018/08/09)
Phosphonates, azoles and quinones are pharmacophores found in bioactive compounds. A series of phosphonates conjugated to azoles and quinones with variable carbon chain lengths were synthesized in 3–4 steps with good yield. Antifungal assay of these compounds showed that ethyl protected phosphates have excellent inhibitory activity against phytopathogenic fungus Fusarium graminearum, and the free-base phosphates have good activity against human pathogenic fungi Aspergillus flavus and Candida albicans. Structure- activity relationship (SAR) studies showed activity increases with longer carbon chain length between phosphonate and anthraquinone analogs consisting of azole and quinone moieties. These newly synthesized compounds also have mild antibacterial activities to Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Cytotoxicity analysis of these compounds against HeLa cells reveals that the phosphoric acid analogs are less toxic compared to ethyl protected phosphonates. Three leads compounds have been identified with prominent antifungal activity and low cytotoxicity.
The effect of chain length and unsaturation on Mtb Dxr inhibition and antitubercular killing activity of FR900098 analogs
Jackson, Emily R.,San Jose, Géraldine,Brothers, Robert C.,Edelstein, Emma K.,Sheldon, Zachary,Haymond, Amanda,Johny, Chinchu,Boshoff, Helena I.,Couch, Robin D.,Dowd, Cynthia S.
, p. 649 - 653 (2014/01/23)
Inhibition of the nonmevalonate pathway (NMP) of isoprene biosynthesis has been examined as a source of new antibiotics with novel mechanisms of action. Dxr is the best studied of the NMP enzymes and several reports have described potent Dxr inhibitors. M
