Zidovudine (AZT) was the first nucleoside analogue licensed for the treatment of HIV infection. Efforts have continuously been made to improve the therapeutic characteristics of this drug, most of them focussed on prodrugs design. Here we describe the anti-HIV-1 activity and cytotoxicity of six novel AZT derivatives namely 3'-azido-3'-deoxy-5'-O-oxalyl-N-valinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-leucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-isoleucinethymidine, 3'-azido-3'-deoxy-5'-O-oxalyl-N-phenylalaninethymidine, 3'-azido-3'-deoxy-5'-O-oxalylthymidine acid, 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine and 5-chloro-6-hydroxy-5,6-dihydro-3'-azido-3'-deoxythymidine which were perfectly characterized. AZT-Val, AZT-Leu, AZT-iLeu, AZT-Phen, AZT-Ac and AZT-Iso have shown a similar or higher selectivity index than that of AZT itself, in one or both of the different cell cultures used (PBMC and MT2). However, AZT-ClOH showed no anti-HIV activity. These results suggest that using amino acids in the design of AZT derivatives improves AZT activity.

2002-04-15·Nucleosides, Nucleotides & Nucleic Acids4区 · 生物学

SYNTHESIS AND IN VITRO ANTIBACTERIAL ACTIVITY OF NOVEL 5′-O-ANALOG DERIVATIVES OF ZIDOVUDINE AS POTENTIAL PRODRUGS

4区 · 生物学

Article

作者: Bogdanov, Patricia M. ; Briñón, Margarita C. ; Moroni, Guillermo N.

An efficient, short synthesis of four potential prodrugs of 3'-azido-3'-deoxythymidine (AZT) and their antibacterial activity are reported. The 5'-OH group of AZT was functionalized with oxalyl chloride obtaining an acyl chloride derivative (AZT-Ox), which by further transformation with leucine, isoleucine and valine amino acids led to the corresponding AZT analogs, namely AZT-Leu, AZT-iLeu and AZT-Val. A carboxyl acid derivative (AZT-Ac) was also obtained by hydrolysis of AZT-Ox. These compounds, which exhibit anti HIV activity, have killed collection and clinical strains of some opportunistic infectious agents in AIDS-related complex. Thus, the clinical strains, K. oxytoca, S. typhi and K. pneumoniae, and collection strain K. pneumoniae ATCC 10031 showed sensitivity to antibiotics. The activity order for the studied compounds against the most sensitive strain (K. pneumoniae ATCC 10031) was AZT-Leu > AZT-iLeu > AZT-Val > AZT-Ac > AZT. On the other hand, the activity order for the second most sensitive strain (K. oxytoca) was AZT-Leu > AZT-Val = AZT-Ac > AZT-iLeu > AZT. The most effective antibacterial drug AZT-Leu, M.I.C.=0.125 microgmL(-1)) was 16 times more active than AZT (AZT, M.I.C.=2 microg mL(-1)) against K.

1993-05-01·The Journal of Clinical Endocrinology & Metabolism

Effect of low dose infusions of ile-atrial natriuretic peptide in healthy elderly males: evidence for a postreceptor defect.

Article

作者: A M Richards ; N Gilchrist ; T Yandle ; E A Espiner ; R Sainsbury ; K Or

Low dose infusions of atrial natriuretic peptide (ANP) have significant biological effects in young adults. In view of the accumulating evidence of age-related changes in ANP physiology, we investigated the effects of a 2-h low dose infusion of ile12-ANP (1.5 pmol/kg/min) in eight healthy, supine, normotensive elderly men in a single blind, random order, placebo-controlled study. Calculated MCR of ANP was 3.3 +/- 0.4 L/min, disappearance half-life 4.1 +/- 0.4 min, and volume of distribution 21 +/- 4 L. The ile-ANP infusions induced the expected significant (3-fold) increases in plasma ANP immunoreactivity in association with enhancement of both plasma and urine cyclic guanosine monophosphate. Despite this, there were no measurable natriuretic effects or changes in blood pressure, and the activities of the renin-angiotensin-aldosterone and sympathetic nervous systems were unchanged. These findings suggest an abnormality in the post-cyclic guanosine monophosphate effector of ANP among elderly normotensive men.

100 项与 Isoleucine-atrial natriuretic factor 相关的药物交易

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