Simultaneous high-performance liquid chromatographic determination of a rhein-diclofenac prodrug and its active compounds.

In order to study the hydrolytic characterization of an anti-inflammatory prodrug (RD-1) in vitro, a simple, specific, precise and accurate method for the simultaneous determination of prodrug and its two hydrolytic active compounds was development using reverse phase high-performance liquid chromatography (RP-HPLC). The chromatographic separation was performed on an ODS-2 C18 column (250 mm x 4.6 mm, 5.0 microm particle size) with a simple elution programme. The mobile phase was methanol-0.1%phosphoric acid solution (adjusted pH to 2.3) (80:20, v/v); wavelength of 257nm and mobile phase flow rate of 1.0 mL/min was utilized for the quantitative analysis. Excellent linear behaviors over the investigated concentration ranges were observed with the values of R2 higher than 0.999 for all the analytes. The validated method was successfully applied to the simultaneous determination of prodrug and its active components.

S-4-Chloro-phenyl 9,10-dihydro-acridine-9-carbothio-ate.

In tricyclic fragment of the title mol-ecule, C(20)H(14)ClNOS, the central 1,4-dihydro-pyridine ring adopts a boat conformation while the two benzene rings form a dihedral angle of 17.38 (5)°. In the crystal structure, weak inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains propagating along the b axis.

Bone-targeting glycol and NSAIDS ester prodrugs of rhein: synthesis, hydroxyapatite affinity, stability, anti-inflammatory, ulcerogenicity index and pharmacokinetics studies.

Although rhein and NSAIDs are potent anti-inflammatory drugs, their use has been limited by the high incidence of gastrointestinal erosions and the necessity to deliver the drug to specific sites of target organ. Using the prodrug approach, a series of rhein-NSAIDs prodrugs containing anthraquinone bone-targeting moiety were synthesized by linking rhein with NSAIDs through glycol ester. The target compounds demonstrated significant capability of binding to HAP and were hydrolytically activated in physiological conditions. Hybrid rhein-NSAIDs prodrugs exhibited significant anti-inflammatory activity, moreover, the tested compounds were also found to possess less degree of ulcerogenic potential. Our pharmacokinetic studies of 7e demonstrated this prodrug is a potential candidate for a slower and sustained release form of rhein.

Synthesis of anthraquinone-ibuprofen prodrugs with hydroxyapatite affinity and anti-inflammatory activity characteristics.

The synthesis and pharmacological activities of anthraquinone-ibuprofen prodrugs for finding new anti-inflammatory drugs specifically targeting osseous tissues were studied. Two hydrolytically activated anti-inflammatory prodrugs containing anthraquinone moiety and ibuprofen moiety were designed and synthesized. Rhein was chosen as bone-targeting agent and potentially active drug, which was linked chemically with ibuprofen through glycol ester as bone-targeting anti-inflammatory prodrugs. The chemical structures of the new compounds were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. The studies of bioactivities demonstrated that both prodrugs showed significant binding capability to hydroxyapatite (HAP), the major component of bone, and were hydrolytically activated under physiological conditions in vitro and better anti-inflammatory activity in vivo.

Characterization and expression profiling of tyrosine aminotransferase gene from Salvia miltiorrhiza (Dan-shen) in rosmarinic acid biosynthesis pathway.

A novel tyrosine aminotransferase gene (designated as SmTAT) involved in rosmarinic acid biosynthesis pathway is cloned from Salvia miltiorrhiza Bung. The full-length cDNA of SmTAT is 1,603 bp long with an open reading frame (ORF) of 1,233 bp encoding a polypeptide of 411 amino acid residues. The deduced amino acid sequence of the SmTAT gene shared high homology with other known TATs. Analysis of SmTAT genomic DNA reveals that it contains 6 exons, 5 introns. The analysis of SmTAT promoter region and terminator region was also presented. Semi-quantitative RT-PCR analysis reveals that the constitutive expression of SmTAT in stem is much higher than that in root, leaf. Further expression analysis reveals that the signaling components of defense/stress pathways, such as methyl jasmonate (MeJA), abscisic acid (ABA), salicylic acid (SA) and ultraviolet-B radiation (UV-B), up-regulate the SmTAT transcript levels over the control. This study provides useful information for further studying this gene and its function in rosmarinic acid biosynthetic pathway in S. miltiorrhiza, the roots of which so-called ''Danshen'' possess many pharmaceutical properties for human health.