Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED<sub>50</sub> values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.
http://ift.tt/2c1v1yf
http://ift.tt/2bNND98
Ιατρική : Τα αισθητικά συστήματα της όρασης,ακοής,αφής,γεύσης και όσφρησης.
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: April 2017 Source: European Journal of Vascular and Endovascular Surgery, Volume 53, Issue 4 http://ift.tt/2oUTFL8 ...
-
Publication date: Available online 8 April 2017 Source: European Journal of Vascular and Endovascular Surgery Author(s): M. Venermo, K. Ma...
-
Related Articles Identification of somatic TERT promoter mutations in familial non-medullary thyroid carcinomas (FNMTC). Clin Endocri...
-
Correlation Between the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test in Patients With Narcolepsy Participating in Two Cl...
-
AbstractBackground Little is known about patterns of medication use and lifestyle counseling in patients with peripheral artery disease (PA...
-
Stereotact Funct Neurosurg 2017;95:69 http://ift.tt/2lpc3FI http://ift.tt/2mcIz2i
-
# Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174, alsfakia@gmail.com , T...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου