Synthesis and anticancer activity of 3-amino-N-phenyl-1H-indazole-1-carboxamide and 1-(1H)indazol-3-yl-3-phenylureido derivatives

Synthesis of New Pyrazole Derivatives as Potential CDK1 Inhibitors

Multi or Single-Kinase Inhibitors to Counteract Drug Resistance in Cancer: What is New?

The concept of protein kinase inhibition starts from the groundbreaking research on the role of these proteins in the regulation of fundamental processes, including proliferation, cell cycle, apoptosis, metabolism, and inflammation. Kinase genetic mutations, as well as overexpression and dysregulation, can contribute to the development of several diseases, including neoplasms, leading to relapses and resistance to standard drug chemotherapy [1-3].

Curcumin derivatives as inhibitors of Gram positive and Gram negative biofilm formation

Paracentrin1, a synthetic antimicrobial peptide fragment of a beta-thymosin from the sea-urchin Paracentrotus lividus, interferes whith staphylococcal and Pseudomonas aeruginosa biofilm formation

Pyrrolomycins as novel agents against staphylococcal biofilms

Synthesis and biological evaluation of some new 2-phenylpropiolamidobenzamides as potential antagonists of the HDM2-p53 protein-protein interactions

Novel chemical countermeasures against staphylococcal biofilms

Some natural and synthetic related pyrrolomycins, a family of halogenated pyrrole antibiotics, showed anti-biofilm properties in vitro at low concentration (0.045μg/mL) against preformed staphylococcal biofilms. Moreover, considering the human cell toxicity, the selectivity indexes (ratio of cytotoxicity to antibiofilm activity) of some of them were very interesting. The present study aims to investigate if the pyrrolomycins could also prevent staphylococcal biofilm formation. The evaluation of S.aureus ATCC 25923 biofilm formation inhibition was conducted by safranin staining method. At tested concentrations of 0.18, 0.09, 0.045 μg/mL (concentrations much lower than MIC value determined on…

SYNTHESIS AND ANTIPROLIFERATIVE ACTIVITY OF 3-AMINO-N-PHENYL-1H-INDAZOLE-1-CARBOXAMIDES

Recently our research group has reported the synthesis of some 3-amino-N-phenyl-1H-indazole-1-carboxamides able to inhibit at low micromolar concentrations the cell growth of many neoplastic cell lines. The above compounds are unsubstituted in the indazole nucleus and this gives the hope to obtain more active compounds if appropriate substituents are beared by the above nucleus. So, several new N-phenyl-1H-indazole-1-carboxamides 1c-h and 4l,m were prepared by reacting phenyl isocyanates 3a,b with 3-amino-1H-indazoles 2c,e,g, or 1H-indazole 2l respectively. Chemical trasformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamides 5a,b, and 3,5-diamino-N-phenyl-…

2-cinnamamido, 2-(3-phenylpropiolamido) and 2-(3-phenylpropanamido)benzamides: synthesis, antiproliferative activity and mechanism of action

Several new 2-cinnamamido, 2-(3-phenylpropiolamido) and 2-(3-phenylpropanamido)benzamides were synthesized by stirring in pyridine the opportune acid chlorides with the appropriate anthranilamide derivatives. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).

Synthesis, antiproliferative activity, and mechanism of action of new benzamido derivatives

The cinnamoyl anthranilamides represent a class of biological active substances of great importance in medicinal chemistry. Moreover, despite their wide range of biological activities, a review of the literature revealed that no anticancer activity is described for this kind of substances. Starting from the 2-cinnamamido-5-iodobenzamide, resulted able to inhibit the leukemic cell line K-562 proliferation with a percent of inhibition of 74% at 10M concentration, we undertake the following structural modifications on cinnamamidobenzamide skeleton: the introduction of various substituents both on the benzamido and the cinnamamido moieties, the substitution of olefinic bond with the ethane, et…

Oregano essential oils activity against Listeria monocitogenes biofilms

Synthesis and Antiproliferative Activity of a New Pyrazolo[3,4-f]1,2,3,5-tetrazepin-4(3H)-one Derivative

CDK: LigandFit Enrichment Plot of Active Compounds in a Screening Dataset.

Synthesis and antioproliferative activity of new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]azepino[4,5-f]azocine

By reacting methylaminopyrazoles with hexane-2,5-dione in 1,4-dioxane in the presence of p-toluensulfonic acid, new derivatives containing the policyclic sistem 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3'.4':2,3]azepino[4,5-f]azocine were obtained. The new synthesized compounds were tested preliminarly at 10 microM against five human cancer cell lines showing a range of inhibition of 20-62% against the most susceptible cell lines K562 and HCT116.

Synthesis and antiproliferative activity of indazole derivatives

Indazole nucleus represents a very attractive scaffol to obtain new molecole endowed with antineoplastic activity. On the basis of these literature data we have designed some indazole derivatives such as N-indazolylbenzamides and N-indazolyl-N’-phenylureas as potential CDK1 inhibitors. In fact the above compounds contain the structural feature, common to the majority of CDK inhibitors, requested to make hydrogen bonds with the molecular forks present in the hinge region of CDKs. The N-indazolylbenzamides 1 were obtained by reacting aminoindazoles and substituted benzoylchlorides. Among the synthesized compounds some derivatives 1 resulted to be CDK1 inhibitors showing IC50 values in the ran…

Paracentrin 1, a synthetic antimicrobial peptide fragment of a beta-thymosin from the sea-urchin Paracentrotus lividus, interferes with staphylococcal and Pseudomonas aeruginosa biofilm formation

New Anti-Adhesion Agents In The Development of Antivirulence Drugs

Gram-positive bacteria are a significant cause of nosocomial and community-acquired infections associated with diseases of high morbidity and mortality. Moreover, antibiotic resistance of important Gram-positive pathogens, such as Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis is one of the major worldwide health problems. Over the last decade, many studies have focused on agents that target the virulence of important pathogens without killing or inhibiting their growth therefore imposing limited selective pressure to promote the development and spread of resistance mechanisms [1]enterococci and streptococci, sortase A plays a critical role in Gram-positive bacter…

ATTIVITÀ ANTIPROLIFERATIVA DI UN DERIVATO POLICICLICO CON STRUTTURA COMPLESSA

Un nuovo derivato policiclico glicosilato è stato ottenuto partendo dal derivato policiclico iodurato, utilizzando la reazione di Sonogashira.Il composto glicosilato saggiato presso l’NCI è risultato attivo su tutte le 60 linee cellulari tumorali del panel, risultando più attivo degli altri composti policiclici precedentemente saggiati. Il composto induce l’arresto del ciclo cellulare in fase G2/M nella linea cellulare MDA-MB231, fa diminuire i livelli di ciclina B1e Cdc-2 mentre produce un aumento dell’inibitore p21WAF1, una chinasi ciclino-dipendente.

Synthesis and biological evaluation of new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides

Synthesis of New Indazol-3-yl derivatives as CDK1 inhibitors

Biofilm capability of staphylococcus strains isolated from food and the anti-biofilm activity of a chemically synthesized pyrrolomycin


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Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-trifluoromethyl-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-one

Synthesis and antiproliferative activity of a natural like glucosyl polycyclic compound

A new polycylic compound was synthesized and evaluated for its antiproliferative activity against the NCI panel of human tumoral cell lines showing IC50 values in the range 0.47-5.43 µM. The compound induced a decrease of the level of cyclin B1, whereas increased the level of the inhibitor p21 WAF1

SYNTHETIC AND BIOLOGICAL EVALUATION OF SOME NEW 2-CINNAMAMIDOBENZAMIDES AS POTENTIAL ANTAGONIST OF THE HDM2-P53 PROTEIN-PROTEIN INTERACTIONS

Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-positive Pathogens: 2-Phenylhydrazonoalkanoic Acid Derivatives

There is an urgent need of anti-virulence agents effective in the prevention or eradication of biofilms that are intrinsically resistant to conventional antibiotics. If we consider that the first step of staphylococcal pathogenesis and of biofilm formation is the bacterial adhesion, promoted by the surface exposed proteins at the cell wall, we believe that new anti-virulence agents could be developed by using as a target the Sortase A (SrtA), the enzyme responsible of linking surface exposed proteins to peptidoglycan. Therefore, SrtA inhibitors could act as anti-adhesion agents useful to prevent Gram positive virulence mechanisms as well as a virulence mechanism based on biofilm formation. …

Pyrazolo[3,4-d]pyrimidine derivatives as COX-2 selective inhibitors: synthesis and molecular modelling studies.

The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin- 4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5- benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5- aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a–d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological result…

BENZOTRIAZINONE AND QUINAZOLINONE DERIVATIVES AS COX-INHIBITORS: COMPUTATIONAL STUDIES

Antileukemic activity of some new 3-amino-N-phenyl-(1H)-indazole-1-carboxamide derivatives

Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamide derivatives