80498-67-5Relevant academic research and scientific papers
Small Molecule Inhibitors of Ca2+-S100B Reveal Two Protein Conformations
Cavalier, Michael C.,Ansari, Mohd. Imran,Pierce, Adam D.,Wilder, Paul T.,McKnight, Laura E.,Raman, E. Prabhu,Neau, David B.,Bezawada, Padmavani,Alasady, Milad J.,Charpentier, Thomas H.,Varney, Kristen M.,Toth, Eric A.,MacKerell, Alexander D.,Coop, Andrew,Weber, David J.
, p. 592 - 608 (2016/02/09)
The drug pentamidine inhibits calcium-dependent complex formation with p53 (CaS100B·p53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of CaS100B·inhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the "FF-gate". For symmetric pentamidine analogues (CaS100B·5a, CaS100B·6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue (CaS100B·17), this same channel was open. The CaS100B·17 structure illustrates, for the first time, a pentamidine analog capable of binding the "open" form of the "FF-gate" and provides a means to block all three "hot spots" on CaS100B, which will impact next generation CaS100B·p53 inhibitor design.
On the reactivity of hydroximoyl chlorides preparation of 2-arylimidazolines
Salgado-Zamora, Hector,Campos, Elena,Jimenez, Rogelio,Cervantes, Humberto
, p. 1043 - 1049 (2007/10/03)
Elimination of the hydroxylamino portion in arylhydroximoyl chlorides upon nucleophilic addition of ethylenediamine rendered an alternative procedure for 2-arylimidazolines preparation.
Analogues of 1,5-bis(4-amidinophenoxy)pentane (pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia
Tidwell,Jones,Geratz,Ohemeng,Cory,Hall
, p. 1252 - 1257 (2007/10/02)
A series of 33 analogues of the anti-Pneumocystis carinii drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) was synthesized for screening against a rat model of P. carinii pneumonia (PCP). Twenty-five of the compounds showed efficacy against PCP when compared to a saline-treated control group. Two compounds, 1,4-bis(4-amidinophenoxy)butane (butamidine, 6) and 1,3-bis(4-amidino-2-methoxyphenoxy)propane (DAMP, 16), were statistically more effective than the parent drug in treating PCP in the rat model of infection. In addition to their activity against PCP, the compounds were also evaluated for antitrypsin activity, ability to inhibit thymidylate synthetase, affinity for DNA, and toxicity. No correlation was observed between the tested molecular interactions of the diamidines and their effectiveness against PCP.
