Synthesis of a Phosphoserine Mimetic Prodrug with Potent ..

The drug (indomethacin) was esterified with paracetamol to prepare mutual prodrug.

Open Archive Synthesis of a Phosphoserine Mimetic Prodrug with ..

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

Specifically, dihydroxyacetone phosphate (DHAP), which is produced during glycolysis, is the precursor for TAG synthesis in adipose tissue.

Expected and observed mechanisms of acyl phosphate nucleoside ..

Purpose: Prostaglandin E1 (PGE1) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE1 in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. Methods: In order to encapsulate PGE1 in nanoparticles prepared with a poly(lactide) homopolymer (PLA) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA), we synthesized a series of PGE1 phosphate derivatives and tested their efficacy. Results: Among them, PGE1 2-(phosphonooxy)ethyl ester sodium salt (C2) showed the most efficient hydrolysis to yield PGE1 in human serum. An in vitro platelet aggregation assay showed that C2 inhibited aggregation only after pre-incubation in serum, suggesting that C2 is a prodrug of PGE1. In vivo, intravenous administration of C2 caused increase in cutaneous blood flow. In the presence of zinc ions, all of the synthesized PGE1 phosphate derivatives could be encapsulated in PLA-nanoparticles. Use of l-PLA instead of d,l-PLA, and high molecular weight PLA resulted in a slower release of C2 from the nanoparticles. Conclusions: We consider that C2-encapsulated nanoparticles prepared with l-PLA and PEG-d,l-PLA have good sustained-release profile of PGE1, which is useful clinically.

Determination of Partition-Coefficient
The partition coefficients of synthesized prodrugs were determined in three systems i.e. octanol-water, octanol hydrochloric acid buffer (pH 1 .2) and octanol-phosphate buffer (pH 7.4) at 25°C temperature. Synthesized compound (100 mg) was added to 10 mL of aqueous phase and 10 mL of organic phase was added to it. This mixture was shaken for 1 h and left for 2 h at 25°C. Layers were separated out using separating funnel. Prodrug concentration in aqueous phase, in hydrochloric acid buffer (pH 1.2) and phosphate buffer (pH 7.4) was determined by HPLC method as detailed earlier after suitably taking into organic phase. The partition co-efficient was calculated as, partition coefficient = concentration of drug in organic phase/that in aqueous phase. The obtained results are shown in .


Benzoyl peroxide/clindamycin - Wikipedia

N2 - The original synthesis of combretastatin A-2 (1a) was modified to provide an efficient scale-up procedure for obtaining this antineoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by phosphorylation employing in situ formation of dibenzylchlorophosphite followed by cleavage of the benzyl ester protective groups with bromotrimethylsilane to afford the phosphoric acid intermediate 11. The latter was immediately treated with sodium methoxide to complete a practical route to the disodium phosphate prodrug (2a). The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts (2a-q) was evaluated with respect to relative solubility behavior, cancer cell growth inhibition and antimicrobial activity.

glyceryl tristearate, 555-43-1 - The Good Scents …

AB - Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

Journal of Nanoscience and Nanotechnology

N2 - Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti-apoptotic activity in both invitro and invivo models. However, its utility is hampered by limited aqueous solubility. As such, water-soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such as decreasing damage from stroke or acute kidney injury. Five phosphate prodrugs were synthesized, including one incorporating a novel phosphoryloxymethyl carboxylate (POMC) moiety. These prodrugs were highly water-soluble, but showed significant differences in chemical stability, with oxymethylphosphate prodrugs being the most unstable. In a series of NMR experiments, the POMC prodrug was bioactivated to UDCA by alkaline phosphatase (AP) faster than a prodrug containing a phosphate directly attached to the alcohol at the 3-position of UDCA. Both of these prodrugs showed significant anti-apoptotic activity in a series of invitro assays, although the POMC prodrug required the addition of AP for activity, while the other compound was active without exogenous AP.