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Biomedical subjects

A Andreani

Publications and source records attributed to A Andreani.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.

The design, synthesis, and rapid evaluation of a new class of acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.

Acetylcholinesterase↗
PubMed2001

Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles.

A number of selected imidazo[2,1-b]thiazoles entered the screening at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) and one of these compounds, 2-chloro-6-phenylimidazo[2,1-b]thiazole, showed antitubercular activity. On this basis we planned the synthesis of new analogues bearing a substituted ring at the 6 position. For one compound only (2-chloro-6-p-chlorophenylimidazo[2,1-b]thiazole) the 5-nitroso derivative was also prepared. The antitubercular activity of these compounds was compared with the known analogues lacking the chlorine at the 2 position. 5-Nitroso-6-p-chlorophenylimidazo[2,1-b]thiazole showed potent antitubercular activity.

Antitubercular Agents↗
PubMed2000

4-Aminopyridine derivatives with antiamnesic activity.

Acetylcholine (Ach) enhancement, useful in the treatment of Alzheimer's disease (AD), may be obtained by means of ion channel modulators such as 4-aminopyridine (4-AP). 4-AP is also the central ring of tacrine, the first drug approved for the treatment of AD. The synthesis and pharmacological activity of three 4-AP derivatives, prepared with the aim of improving their antiamnesic activity, is here described. In two of these compounds 4-AP is connected to 4-aminobutyric acid (GABA), whereas in the third it is connected to 2-indolinone, i.e., the skeleton of linopirdine, another Ach enhancing agent. The new compounds showed potent antiamnesic activity in comparison with piracetam.

4-Aminopyridine↗
PubMed2000

Potential antitumor agents. Part 29(1): synthesis and potential coanthracyclinic activity of imidazo[2,1-b]thiazole guanylhydrazones.

This paper reports the synthesis of new imidazo[2,1-b]thiazole guanylhydrazones which were tested as potential antitumor agents. Three of these derivatives (those bearing a 3- or 4-nitrophenyl group) were the most potent and one of these showed a mild effect as CDK1 inhibitor. These same three derivatives were also tested as positive inotropic agents and two of them were more potent than amrinone at 10(-5) M. These two guanylhydrazones could be useful coanthracyclinic agents.

Animals↗
PubMed2000

Imidazo[2,1 -b]thiazolylmethylene- and indolylmethylene-2-indolinones: a new class of cyclin-dependent kinase inhibitors. Design, synthesis, and CDK1/cyclin B inhibition.

Compounds containing a 2-indolinone moiety linked to imidazothiazole and indole fragments were studied as cyclin-dependent kinase inhibitors. The activity of all the new derivatives was tested in vitro against CDK1/cyclinB and the selectivity towards two other kinases was determined for the most promising compounds. The binding mode of one representative compound was investigated by means of a three-dimensional model of the inhibitor-CDK1 complex. The work allowed us to identify (2-chloroindolyl)methylene-2-indolinone as a new lead of a class of CDK1/cyclinB inhibitors, whose potency can be improved by the introduction of suitable variations on the basic molecular skeleton.

Binding Sites↗
PubMed1998

In vivo cardiotonic activity of aryl- and pyridyl-substituted fused imidazoles.

Two new imidazo[2,1-b]thiazoles related to sulmazole were synthesized and subjected to an in vivo cardiotonic assay with 14 analog compounds which gave the best results in previously reported in vitro tests. The data obtained show that three substituents (3-pyridyl, 4-pyridyl and 2,5-dimethoxyphenyl group) are useful pharmacophoric groups in modulating the in vivo cardiotonic activity of the fused imidazoles considered.

Animals↗
PubMed1998

In vivo cardiotonic activity of pyridylmethylene-2-indolinones.

The synthesis of 5-chloro-3-pyridylmethylene-2-indolinone is reported. This compound was subjected to an in vivo cardiotonic assay with 10 analogs whose synthesis and in vitro cardiotonic activity were previously reported. All the compounds tested (except the 5-hydroxyindole derivative) showed significant positive inotropic activity. The 3-pyridyl derivative without substituents at the indole system was the most active of the whole series.

Animals↗
PubMed1996

Potential antitumor agents. 24. Synthesis and pharmacological behavior of imidazo[2,1-b]thiazole guanylhydrazones bearing at least one chlorine.

In connection with a previous research dealing with the antitumor activity of imidazo[2,1-b]-thiazole guanylhydrazones, this paper reports the synthesis of new derivatives which were tested for antitumor and positive inotropic activity. In most cases the cytotoxic data from the in vitro experiments (HeLa) were in agreement with the antitumor data in vivo (Ehrlich). The active compounds bear a phenyl ring at the 6 position. On the other hand, the most active cardiotonic agents were devoid of the phenyl ring.

Animals↗
PubMed1995

Thienylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase.

The synthesis of 6-substituted 5-(thienylvinyl)imidazo[2,1-b]thiazoles and 6-thienylimidazo[2,1-b]thiazoles is reported. These compounds were tested as specific inhibitors of the NADH: ubiquinone (UBQ) reductase activity of NADH dehydrogenase in mitochondrial membranes. The 6-thienylimidazo[2,1-b]thiazoles were more potent in mammalian than in nematode mitochondria and had an average titer of 0.11 mM for 2-methyl-6-(2-thienyl)imidazo[2,1-b]thiazole (10). This compound is noncompetitive with the ubiquinone substrate and interacts with a site which is mutually exclusive with that of rotenone but nonexclusive with that of piericidin and several other inhibitors of NADH dehydrogenase. In the series of 5-(thienylvinyl)imidazothiazoles, the hydrobromide of (E)-6-chloro-5-(2-thienylvinyl)imidazo[2,1-b]thiazole (E-5.HBr) was found to be more potent as an inhibitor of the NADH:UBQ activity (IC50 = 15-17 microM) than the 6-thienylimidazoles such as 10. The inhibitory action of E-5.HBr and its analogs is different from that of compound 10 as indicated by the mutual exclusivity with other inhibitors and the relative inhibition of the activity with various electron acceptors.

Animals↗
PubMed1994

Thienylvinylindoles as inhibitors of mitochondrial NADH dehydrogenase.

In connection with a previous study, new phenylindoles bearing a 2- or 3-thienyl group were synthesized and tested as specific inhibitors of mitochondrial NADH dehydrogenase. The position of the phenyl ring and the geometrical configuration play an important role in the activity and specificity of these derivatives. In order to study the mechanism of action of these thienylvinylindoles, their activity was compared with that of known inhibitors in a new test employing exogenous quinones.

Animals↗
PubMed1993

Potential antitumor agents. XX (1). 6-Anilinoimidazo[2,1-b]thiazoles.

The synthesis of 6-anilinoimidazo[2,1-b]thiazoles, related to the well-known antitumor agent amsacrine, is reported. The cytotoxic activity of the new compounds was evaluated on HeLa cells. Compound 3a, the most closely related to amsacrine, was significantly active.

Antineoplastic Agents↗
PubMed1993

Potential antitumor agents. 23.(1) Cytotoxic and differentiating activity of compounds related to hexamethylenebisacetamide.

The synthesis of potential differentiating agents related to hexamethylenebisacetamide (HMBA) is reported. 1,6-Bis(3,3-dimethyl-2-oxo-2,3-dihydroindol-1-yl)hexane (4) and 1,6-bis(4-carbamoyl-thiazol-2-yl)hexane (9) were not soluble enough to allow biological testing. For this reason the dipotassium salt (10) of 1,6-bis(4-carboxy-thiazol-2-yl)hexane (11) was prepared. The salt 10, tested in the human rhabdomyosarcoma cell line (RMZ) and in the murine Friend erythroleukemia cells (MEL), proved more cytotoxic than HMBA, but was devoid of differentiating activity. Compounds 4, 9, 10 and 11, tested on HeLa cells (in vitro) and on Ehrlich ascites (in vivo) did not show antitumor activity.

Acetamides↗