9-(4'-Phosphonomethoxy-2'-cyclopenten-1'-yl)hypoxanthine and 9-(4'-phosphonomethoxy-2',3'-dihydroxycyclopenten-1'-yl)hypoxanthine were synthesized as isosteric carbocyclic analogues of inosine-5'-monophosphate. The synthesized compounds were shown to be capable of inhibiting the activity of human type II inosine-5'-monophosphate dehydrogenase (IMPDH II) (IC(50 )= 500 µM) and to have no significant effects on the growth ofMycobacterium tuberculosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549521PMC

Publication Analysis

Top Keywords

carbocyclic analogues
8
analogues inosine-5'-monophosphate
8
inosine-5'-monophosphate synthesis
4
synthesis biological
4
biological activity
4
activity 9-4'-phosphonomethoxy-2'-cyclopenten-1'-ylhypoxanthine
4
9-4'-phosphonomethoxy-2'-cyclopenten-1'-ylhypoxanthine 9-4'-phosphonomethoxy-2'3'-dihydroxycyclopenten-1'-ylhypoxanthine
4
9-4'-phosphonomethoxy-2'3'-dihydroxycyclopenten-1'-ylhypoxanthine synthesized
4
synthesized isosteric
4
isosteric carbocyclic
4

Similar Publications

Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591).

View Article and Find Full Text PDF

In vitro relative cytotoxicity (IC ()/IC () of ()-3-(4'-methylbenzylidene)-4-chromanone () towards human Molt 4/C8 and CEM T-lymphocytes showed a >50-fold increase in comparison to those of the respective tetralone derivative (). On the other hand, such an increase was not observed in the analogous 4-OCH ( and ) derivatives. In order to study whether thiol reactivity-as a possible basis of the mechanism of action-correlates with the observed cytotoxicities, the kinetics of the non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of and were investigated.

View Article and Find Full Text PDF
Article Synopsis
  • - A new series of synthetic compounds, based on natural (5Z,9Z)-diene acids and containing an oleanolic acid fragment, was created by linking it to different amines and a specific carboxylic acid using innovative chemical reactions.
  • - The synthesized compounds showed significant cytotoxic effects against various cancer cell lines, with one compound demonstrating the strongest activity, indicated by low IC50 values in tests on Jurkat, K562, U937, and HEK293 cells.
  • - One of these compounds was found to trigger apoptosis (programmed cell death) and exhibit genotoxic effects in Jurkat cell cultures, suggesting its potential as a promising candidate for antitumor drug development.
View Article and Find Full Text PDF

A bioassay-guided chemical investigation of an Australian pasture-soil-derived sp. yielded the rare carbocyclic -polyketide kendomycin () along with a series of new analogues, goondomycins A-H (-), featuring unprecedented carbo/heterocyclic scaffolds and chromophores, with structures assigned by detailed spectroscopic analysis, chemical and biochemical transformations, and biosynthetic considerations. Goondomycins B () and F () are noteworthy in being potent motility inhibitors of heartworm microfilaria (EC 0.

View Article and Find Full Text PDF

The melanocortin 4 receptor (MC4R) plays a critical role in satiety and energy homeostasis, and its dysregulation is implicated in numerous hyperphagic and obese disease states. Setmelanotide, a disulfide-based cyclic peptide, can rescue MC4R activity and treat obesities caused by genetic defects in MC4R signaling. But this peptide has moderate blood-brain barrier penetrance and metabolic stability, which can limit its efficacy in practice.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!