A series of androst-5-ene-4,7-diones and 4-oxygenated androst-5-enes were synthesized and tested for their ability to inhibit aromatase in human placental microsomes. All of the steroids examined inhibited the enzyme in a competitive manner. The inhibitory activity of 4β-hydroxy-5-ene steroid 7...

Reaction of androst-5-en-17-one (1) with hypobromous acid using a short reaction time (30 min) along with a careful isolation procedure gave, for the first time, the addition product, 5α-bromo-6β-hydroxyandrostan-17-one (3), in 43% yield. This bromohydrin was much more reactive than 5α-brormo...

The present work describe the synthesis of a novel series of celecoxib derivatives (6a-m) and they were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA I, II, IV and IX which are involved in a variety of diseases such as glaucoma, retinitis pigmento...

A class of 9(10H)-acridone derivatives with terminal ammonium substituents at C2 (and C7) position(s) on the acridone ring were successfully synthesized. The relative affinities of the acridone compounds to G-quadruplex DNA have been investigated and the results showed that these compounds had a...

ABSTRACTA series of 2-[2-(2,6-dichlorophenyl)amino]benzyl-3-(5-substituted phenyl-4,5-dihydro-1H-pyrazol-3-yl-amino)-6,8-dibromoquinazolin-4(3H) ones 6a-m have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl) amino]benzyl-3-substituted phenylacrylamido-6,8-dibromoquinazolin-4(3H) on...

The reaction of 4-(methylsulfonyl)phenylacetohydrazide (3) with carbon disulfide and potassium hydroxide followed by hydrazine hydrate gave 4-amino-5-[4-(methylsulfonyl)benzyl]-4H-[1,2,4]triazole-3-thione (4). The resulting triazole was subjected to cyclocondensation reaction with different phen...

In previous work, we described 6-6‘-bisindole compounds targeting a hydrophobic pocket on the N-heptad repeat region of viral glycoprotein-41 as effective inhibitors of HIV-1 fusion. Two promising compounds with sub-micromolar IC50's contained a benzoic acid group and a benzoic acid ester ...

The title compound, gem-ketovinylsulfone 3, was obtained stereoselectively (de > 98%) by the action of the α-anion from p-tolylsulfonylacetone 1 on imidazol[1,2-a]pyridine-2-carbaldehyde 2 in chelation-controlled conditions in the presence of a Lewis acid (ZnCl2). The X-ray crystal structure of...

In previous reports, our laboratory has described a drug-responsive NADH oxidase activity of the external surface of the plasma membrane of HeLa and other cancer cells, but not from normal cells, that was shed into media conditioned by the growth of cancer cells such as HeLa and also into sera o...

In this work, a new series of arysulfonylhydrazine-1H-1,2,3-triazole derivatives were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. Among the 1,2,3-triazole derivatives, 1-[(5″-methyl-1″-(4‴-fluorophenylamino)-1H-1,2,3-triazol-4″-yl)carbonyl]-2-(4′...

Right side-out plasma membrane vesicles isolated from HeLa cells exhibited an NADH oxidase activity at their external surfaces that was inhibited by the antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984). Intact HeLa cells (fresh or frozen) also exhibited an N...

Plasma membrane vesicles isolated from HeLa cells grown in suspension culture contain a protein disulfide-thiol interchange (protein disulfide-like) activity. The activity was estimated from the restoration of activity to inactive (scrambled) pancreatic RNAase. RNAase activity was measured eithe...

Proton release from HeLa cells was stimulated by an external oxidant, potassium ferricyanide, or by the growth factor diferric transferrin. This stimulated proton release was inhibited by the antitumor sulfonylurea LY181984 [N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea] over the concentra...

NADH oxidase activity from HeLa plasma membranes was inhibited by the antitumor sulfonylurea N-(4-methylphenylsulfonyl)-N′(4-chlorophenyl)urea (LY181984). With sealed right side-out vesicles, the drug inhibited half maximally at about 30 nM and the inhibition was nearly complete. A closely rela...

Plasma membrane vesicles from HeLa S cells grown in culture bound with high affinity the antitumor sulfonylurea N-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984). Based on binding site protection experiments with the radiolabeled thiol reagent N-[14C]ethylmaleimide, a ca. 34 kDa bin...

The cellular pharmacology of N-(4-methylphenylsulfonyl)-N-(4-chlorophenyl)-urea (MPCU) has been examined in a cloned line of GC3 human colon adenocarcinoma cells. There was a rapid concentrative accumulation of drug, which could be separated into energy-independent and -dependent phases. Accumul...

Topological analysis of the electron density and potential energy density distribution functions in the crystal of 8-dimethylamino-N’,N’-dimethylnaphthalene-1-carboxamide in conjunction with geometrical criteria proposed by J. D. Wallis et al. (J. Chem. Soc., Perkin Trans. 2, 2001, 133), revea...

A novel series of 4-substituted 2-naphthamide derivatives were designed, synthesized and evaluated for their biological activity. In particular, the ability of the compounds to potentiate the action of antibiotics, to inhibit Nile Red efflux and to target AcrB specifically was investigated. The ...

2-Substituted N,N-diethyl or N,N-diisopropyl 1-naphthamides exist as stable atropisomers. When the 2-substituent is a 1-hydroxyalkyl group, the atropisomers are separable diastereoisomers. Synthesis of these compounds by the addition of aldehydes to orholithiated N,N-dialkyl 1-naphthamides proce...

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer’s disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synt...