Lipophilic Character of Novel Zidovudine Derivatives With Antiretroviral Activity.

GUILLERMO N. MORONI, MARIO A. QUEVEDO, SOLEDAD RAVETTI, MARGARITA C. BRIÑÓN.

JOURNAL OF LIQUID CHROMATOGRAPHY AND RELATED TECHNOLOGIES

Marcel Dekker, INC.

Lugar: New York.; Año: 2002 vol. 25 p. 1357 - 1377

1082-6076

The lipophilic properties of a novel series of zidovudine amino acid derivatives were measured using chromatographic techniques, reversed-phase thin layer chromatography (RP--TLC) and reversed-phase high performance liquid chromatography (RP--HPLC), as well as the classic shake flask (log Po/w) and theoretical CLOGP methods. These novel derivatives, obtained by association of zidovudine (AZT) with the essential amino acids leucine (AZT--Leu), isoleucine (AZT--iLeu), phenylalanine (AZT--Phe), valine (AZT-- Val), proline (AZT--Prol) and tryptophane (AZT--Tryp), exhibited an increased log Po/wo/w) and theoretical CLOGP methods. These novel derivatives, obtained by association of zidovudine (AZT) with the essential amino acids leucine (AZT--Leu), isoleucine (AZT--iLeu), phenylalanine (AZT--Phe), valine (AZT-- Val), proline (AZT--Prol) and tryptophane (AZT--Tryp), exhibited an increased log Po/wo/w as compared with the parent compound as follows: AZT--iLeu > AZT--Leu > AZT--Tryp > AZT--Val > AZT--Phe > AZT--Prol > AZT > Thym. All assays were performed using buffer pH 2 as mobile phase, at which the mentioned compounds were complete as their non--ionized forms. In addition, good linear relationships were observed between log P values determined by the shake flask method (log Po/w), and those obtained by chromatographic techniques (log PRP--TLC and log PRP--HPLC) and from theoretical calculations using the CLOGP program (log PCLOGP). These results demonstrate the applicability of the chromatographic methods to describe the lipophilic properties of this family of compounds. o/w), and those obtained by chromatographic techniques (log PRP--TLC and log PRP--HPLC) and from theoretical calculations using the CLOGP program (log PCLOGP). These results demonstrate the applicability of the chromatographic methods to describe the lipophilic properties of this family of compounds. RP--TLC and log PRP--HPLC) and from theoretical calculations using the CLOGP program (log PCLOGP). These results demonstrate the applicability of the chromatographic methods to describe the lipophilic properties of this family of compounds. CLOGP). These results demonstrate the applicability of the chromatographic methods to describe the lipophilic properties of this family of compounds.