SYNTHESIS AND EVALUATION OF AMINO ACID ESTER CONJUGATES OF HIV PROTEASE INHIBITOR

Objective: Ester conjugates of HIV protease inhibitor, lopinavir (LP) with various amino acids were synthesized to improve its physicochemical and pharmacokinetic profile and consequently therapeutic potential. Materials and Methods: Conjugates of LP with amino acids; glycine, alanine, valine, and serine were prepared by dicyclohexylcarbodiimide coupling method. The synthesized compounds were characterized by nuclear magnetic resonance, mass, and Fourier-transform infrared spectroscopy and evaluated for their solubility, partition coefficient, hydrolytic stability, cytotoxicity, and permeability through Caco-2 cells. Results: Aqueous solubility studies indicated significantly better solubility profiles of all conjugates as compared to LP. With respect to hydrolysis, all the conjugates displayed higher stability under acidic conditions while undergo hydrolysis with rise in pH. Conjugates did not exhibit cytotoxicity for concentration as high as 100 μg/ml, which indicates promising therapeutic potential. Absorptive diffusion of drug across Caco-2 cell monolayers was improved by amino acid conjugation. Conclusion: Amino acid ester conjugates of LP not only showed better solubility but also significantly higher permeability than LP. Thus, direct conjugation of L-amino acids is a viable approach to improve oral absorption and thereby oral bioavailability of protease inhibitors

Natural remedies for heart diseases

420-427Heart diseases have posed a great challenge in the developing countries. Heredity, high blood pressure, diabetes, high serum cholesterol, smoking, improper diet and stressful life styles are the factors, which are responsible for heart diseases. In Ayurveda believes that heart diseases are due to the imbalance of three doshas and bringing the normal levels of these tridoshas back to normal will be major step in management of heart diseases. Ayurveda treats heart diseases at two levels; first level is the preventive one and second level deals with the treatment of heart diseases with different plants and their formulations. In the paper, some of the plants and formulations, useful in the treatment of heart diseases have been summarized