ABSTRACT
Some 3-(dialkylamino)-1H-naphtho [2,1-b] pyran-1-ones were tested to evaluate their ability to inhibit Protein Kinase C (PKC) activation. The model consisted in the detection of the superoxide anion in activated neutrophils. Naphthopyrans carrying 3-(diethylamino), 3-(1-piperidinyl) and 3-[bis(2-methoxyethyl)amino] groups emerged as the most active ones. Introduction of alkoxy groups in position 8 and 9 and of bromo substituent in position 8 on the naphthalene moiety was associated with an increase in anti-PKC activity. No activity was found when an electron withdrawing group was placed in position 2 of the 3-(dialkylamino)-1H-naphtho [2,1-b] pyran-1-ones.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Naphthalenes/chemical synthesis , Protein Kinase C/antagonists & inhibitors , Pyrones/chemical synthesis , Enzyme Inhibitors/pharmacology , Humans , In Vitro Techniques , Macrophage Activation/drug effects , Naphthalenes/pharmacology , Neutrophils/drug effects , Neutrophils/enzymology , Pyrones/pharmacology , Structure-Activity Relationship , Superoxides/metabolismABSTRACT
Antisense oligodeoxynucleotides (ODNs) and their derivatives are highly interesting tools to regulate gene expression and promising drugs for antiviral and anticancer therapy. In view of performing more extensive pharmacological trials requiring relatively great amounts of ODNs, we used a method of ODN synthesis derived from the phosphotriester approach which allow to prepare ODNs covalently linking cholesteryl residue (in 5' or 3') and phenazinium group (in 5'). HPLC purifications are discussed.
Subject(s)
Oligonucleotides, Antisense/chemical synthesis , Base Sequence , Chromatography, High Pressure Liquid , Molecular Sequence Data , Oligonucleotides, Antisense/chemistry , Oligonucleotides, Antisense/isolation & purificationABSTRACT
Previous studies showed that some 2'-alkyloxyisoxazoles 2b-d obtained from 3-(diethylamino)-5-(2'hydroxy-4'-methoxyphenyl)isoxazole 2a were endowed with an interesting anti-group B rhinovirus activity (action on HRV-2 serotype). Other isoxazoles (WIN compounds) are well known to have anti-group A rhinovirus activity (action on HRV-14 serotype). To obtain an action similar to that of WIN compounds, starting from 2a, the 2'-acyl (3,4,5) and 2'alkyl (6,8) derivatives were synthesized. Also some Mannich bases (9,10) and bisisoxazoles (7,11,13,14) were studied. Though some of the tested compounds mainly exhibited anti-group B rhinovirus activity, their potency was less intense with respect to the above mentioned compounds 2b-d. The only N-methylpiperazinomethyl derivative 10 was slightly active against both tested serotypes.
Subject(s)
Antiviral Agents/chemical synthesis , Isoxazoles/chemical synthesis , Rhinovirus/drug effects , Antiviral Agents/pharmacology , Cytopathogenic Effect, Viral/drug effects , HIV-1/drug effects , HeLa Cells , Humans , Isoxazoles/pharmacology , Virus Replication/drug effectsABSTRACT
HPLC separation of crude extract components derived from nematocysts and extranematocystic tissues of macroplanktonic jellyfish Aequorea aequorea and Rhizostoma pulmo and benthic sea-anemones Actinia equina and Anemonia sulcata was carried out by different columns. A satisfactory peak separation was obtained analyzing the toxin of Rhizostoma pulmo by cationic and C18 columns. Low molecular weight fragments were separated by C18 column and U.V. monitored varying pH values and obtaining the displacement of significant peaks. Clear differences between chromatographic plots concerning planktonic and benthic species was evidenced by anionic column; this result can point out a clear ecological analogy between species living in the same environment and a similar toxin biosynthesis, due to selective actions related to both the environment and the phylogenetic relationships; these organisms could have developed similar mechanisms useful to tackle the environment.