Medicinal Chemistry

The progress in oral absorption of protein and peptide drugs has been hampered by the difficulty in transporting larger molecules across the gastrointestinal membrane. We are reporting here a study of the design and synthesis of cholic acid-peptide conjugates for peptide drug delivery through gastrointestinal track mediated by bile acid transporter. As principal samples, three small cholic acid-peptide conjugates containing a biodegradable ester bond via threonine linker have been synthesized. In order to introduce ester bond between cholic acid and peptides, conventional solid phase synthesis is not practicable, thus solution phase was employed. The threonine moiety was chosen to introduce a hydroxyl group, on which an ester bond can be formed with different peptides. The threonine moiety also provides the necessary negative charge adjacent to the C24 position as required for transport recognizing by the bile acid transporter in the ilue epicell. The synthetic process was based on DCC chemistry. By using catalytic amounts of N-hydroxysuccinimide the procedure for amide coupling was simplified and shortened while maintaining high efficiency. Esterification using ethyl acetate in the presence of triethylamine selectively introduced an ester bond at the C27 position giving higher yield with no protection on other three hydroxyls. The work also demonstrated that in solution phase synthesis of these peptide conjugates fluoride ion (F-) was more efficient than piperidine to cleave Fmoc from the amino group.

Cell culture experiment showed the efficiencies of transporting of the conjugates and the dissociation of the conjugates detected by HPLC, suggesting that the cholic acid conjugates linked by degradable ester bond can be used as bigger molecule drugs delivering template. Further study would be designed by using more different linkers that would be also biodegradable bonds, such as thioester and so forth.

In this study, a phytochemical analysis was performed, for the first time, on Iris marsica I. Ricci e Colas. In particular, the attention was focused on the constituents of the roots. Twenty-one compounds were isolated by column chromatography and were analyzed/identified by NMR spectroscopy and mass spectrometry. They all own chemotaxonomic, ethno-pharmacological and nutraceutical relevance which allowed us to provide a phytochemical rationale, for the correct botanical classification of this species, for the employment of its roots in folk medicine like for all the other species belonging to the Iris genus and, lastly, for their further uses as food with important healthy benefits. All of these parts were broadly discussed about within the text.

Background: Rabies is a deadly zoonotic viral disease. It is a major public-health problem which presents huge economic and health burdens in most parts of the developing world. The disease is difficult to treat once the clinical manifestations start to develop; the vaccines produced in mammalian neural tissues have the disadvantage of causing severe adverse reactions. This leads to the practice of traditional medicine for the control of rabies in most parts of Ethiopia for many years. Objective: The aim of this review is to give an insight into some of the most commonly used folkloric plants and their method of preparation for the management of rabies. Methods: Data for this review were generated from the published research findings on Ethiopian traditional medicinal plants on indifferent peer reviewed journals and proceedings using search words, Rabies in Ethiopia, medicinal plants, Ethno botanical studies and anti-rabies activity. Descriptive analysis was conducted using excel spreadsheets and the numbers of plants species and families were reported in frequency tables and figures. Results: Results showed that a total of 199 plant species belonging to 47 families were used for the management of rabies. The most commonly used families were ephorbiacea stood first, followed by phytolaceae, cucurbitaceae, acanthracea, fabaceae and solianaceae. Phytolacadodecandra, Justicaschimperiana, Recinuscommunis, Brucea antidysenterica, Croton macrostachyus and Cucumis ficifolius were the most cited medicinal plant species utilized for the management of rabies. The most widely used plant part for the preparations of remedy were roots followed by leaves, used in solution form by using water as a most cited solvent. Conclusions: This review indicated that there are many plants utilized for the management of rabies. Hence further research is recommended for ascertaining the efficacy, safety and quality of the claimed medicinal plants. There is also recommended to strengthen the documentation of the indigenous knowledge which contributes for the drug development used for the management of rabies.