Cyclopentenyl cytidine analogue

Regulation of Cardiolipin Biosynthesis in H9c2 Cardiac Myoblasts by Cytidine 5′-Triphosphate

“…Upon entrance into cells the anti-tumor agent CPEC is rapidly phosphorylated to CPEC mono-, di, and triphosphate, a specific inhibitor of CTP synthetase (23,(31)(32)(33)(34)(35)(36). In the present study, treatment of H9c2 cardiac myoblast cells with CPEC for 12 h caused a reduction in cellular CTP concentration but did not significantly affect the concentration of the other high energy nucleotides ATP, UTP, and GTP.…”

“…Thus, the presence of CPEC specifically reduces the intracellular CTP level, and the presence of cytidine reverses this effect without influencing the level of other cellular nucleotides. CPEC addition to cancer cells was shown to cause a reduction in DNA and RNA synthesis (32). As a control, H9c2 cardiac myoblast cells were incubated in the absence or presence of 5 M CPEC for 12 h and then incubated with [2, H]adenine or [methyl-3 H]thymidine, and the radioactivity incorporated into DNA and RNA was determined.…”

Carbocyclic nucleosides

“…l~~-'~~ On the other hand, neplanocin was not highly cytocidal to HT-29 cells when compared to other adenosine analogues and its principal effect was inhibition of RNA methy1ati0n.l~~ As with C-Ado, it was not a good substrate for AdoHcy-ase and consequently the NucHcy analogue was not apparently formed. 139 This NucHcy metabolite was nevertheless detected as a consequence of a transmethylation reaction that used the NucMet analogue as a methyl donor s p e c i e~. *~~-'~* In fact, this NucMet metabolite appeared to be the principal metabolite in both HT-29 cells as well as in mouse L-929…”

Carbocyclic pyrimidine nucleosides as inhibitors of S-adenosylhomocysteine hydrolase

“…The resulting residue was coevaporated with MeOH (3 × 10 mL) to remove trace amounts of TFA. The resulting residue was then purified using C-18 HPLC eluting 90: 10 …”

“…7-9 Unfortunately their close resemblance to adenosine rendered them susceptible to recognition and phosphorylation by cellular kinases, resulting in significant toxicity. 10 In response to this, strategic removal of the 4′-hydroxymethyl group of Ari and NpcA to afford the 4′,5′-saturated (2) and 4′,5′-unsaturated (4) derivatives proved to be successful, as both were potent inhibitors of SAHase. 11,12 Interestingly, neither served as a substrate for adenosine kinase or adenosine deaminase, thus did not exhibit the toxicity associated with Ari and NpcA.…”