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Research Journal of Pharmacy and Technology
Year : 2020, Volume : 13, Issue : 2
First page : ( 645) Last page : ( 650)
Print ISSN : 0974-3618. Online ISSN : 0974-360X.
Article DOI : 10.5958/0974-360X.2020.00123.7

Synthesis, Hydrolysis kinetics and In-vitro Evaluation of Amino Acid Ester Conjugates of Atazanavir

Dr. Chabukswar A. R.1, Dr. Jagdale S. C.1, Gandhi P. M.2,*

1Department of Pharmaceutical Chemistry, MAEER'S Maharashtra Institute of Pharmacy, Pune-411038, India

2Department of Pharmaceutical Chemistry, JSPM's Jayawantrao Sawant College of Pharmacy and Research, Hadapsar, Pune-411028

*Corresponding Author E-mail: preetigandhi2007@gmail.com

Online published on 9 April, 2020.

Abstract

Purpose

In the present study ester conjugates of a protease inhibitor, Atazanavir (AT) were prepared with various amino acids to improve its physicochemical, pharmacokinetic and safety profile.

Methods

All the conjugates were synthesized by dicyclohexyl carbodiimide (DCC) coupling method using dimethylaminopyridine as a catalyst. The synthesized compounds were characterized by NMR, mass, FTIR spectroscopy and elemental analysis and evaluated for their solubility, partition coefficient and hydrolytic stability. Cytotoxicity and permeability studies were carried out across Caco-2 cell line. The synthesized derivatives were screened for anti-HIV activity by protease inhibition assay.

Results

Solubility studies indicated that all the conjugates have greater water solubility as compared to AT. Conjugates displayed higher stability under acidic conditions while undergo hydrolysis as the pH is increased. Absorptive diffusion across Caco-2 cell monolayers was improved and recognition by efflux carriers was reduced by amino acid conjugation. No cytotoxicity was detected for conjugates upto concentration as high as 100μg/ml, which indicates better safety profile and promising therapeutic potential.

Conclusion

Direct conjugation of L-amino acids has the potential to improve oral absorption and thereby oral bioavailability of protease inhibitors.

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Keywords

Atazanavir, amino acids, conjugate, solubility, hydrolysis, anti-HIV.

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