0000000001179257
AUTHOR
M Tolomeo
Identification of biphenyl-based hybrid molecules able to decrease the intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells.
Synthesis and antiproliferative activities of two new analogs of tetrazepinones
Based on the encouraging results, we report the multistep synthesis and the biologicalo results of two new analogs of tetrazepinones: the 3,5-dimethyl-6-phenyl-8-(trifluoromethyl-5,6-dihydropyrazo1o[3-4-f]1,2,35)tetrazepin-4(3H)-one and the 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl-5,6-dihydropyrazo1o[3-4-f]1,2,35)tetrazepin-4(3H)-one. Both compounds showed a pro-apoptotic activity against HL60 and K562 resistant cell lines. Flow cytometry studies carried out 0n K562 cells allowed to establish that the methyl derivative induces G0-G1, phase arrest followed by apoptosis, whereas the chloroethyl derivative is a not phase-specific agent.
SINTESI ED ATTIVITÀ ANTIPROLIFERATIVA DI NUOVI DERIVATI A STRUTTURA TETRAZEPINONICA
Sintesi di due nuovi composti a struttura tetrazepinonica, analoghi della Temozolomide. I due nuovi composti hanno mostrato una interessante attività antiproliferativa nei confronti di linee cellulari tumorali esprimenti l'enzima MGMT
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-…
Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors
2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis.
Valutazione dell'attività apoptotica di alcuni 3,5-dimetossistilbeni naturali e di sintesi su Leishmania infantum
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…
Cytotoxic effects of polyphenols from waste-water of extra virgin olive oil on human HL60 and K562 cell lines.
Effects of extra virgin olive oil phenols on HL60 cell lines sensitve and resistant to anthracycline
HISTONE DEACETYLASE (HDAC) INHIBITION MODULATES INTRACELLULAR DEOXYNUCLEOTIDES (DNTP) POOLS AND POTENTIATES THE ANTITUMOR EFFECTS OF THE RIBONUCLEOTIDE REDUCTASE (RR) INHIBITOR 3’- METHYL-ADENOSINE (3’-ME-ADO) IN PROMYELOCITIC LEUKAEMIA CELL LINES.
HDAC inhibitors are a new class of antitumor agents that were reported to enhance the cytotoxic effects of a number of classical anticancer drugs through multiple mechanisms. In particular, they are capable of modulating the expression of a series of key cellular genes leading to significant antiproliferative and apoptotic effects. However, which of the possible drug combinations would be the most effective and clinically useful is still to be determined. We treated the HL60 and NB4 promyelocitic leukaemia cells with a combination of the RR inhibitor 3’-Me-Ado and several hydroxamic acid–derived HDAC inhibitors, including the two recently synthesized molecules, MC1864 and MC1879, and the re…
Optimizing tumor-reactive γδ T cells for antibody-based cancer immunotherapy.
Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu(+) breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent functi…
Effect of extra virgin olive oli phenols on HL60 cell lines sensitive and resistant to anthracyclines
Antitumor effects of novel co-drugs linking histone deacetylase and ribonucleotide reductase inhibitors in hematological tumors
Combination therapy is the mainstay of anticancer therapy due to the significant synergistic effects achievable. Now that anticancer drug research turned toward a more molecular targeted approach, the design of dual-target drugs appears to be a new promising strategy with the potential to improve the therapeutic efficacy of the single drug and to reduce the probability of drug induced resistance and cross resistance. In our previous work, we found that 3’-C-methyl-adenosine (3’-Me-Ado), developed by us as a potent ribonucleotide reductase (RR) inhibitor with antitumor activity against both human leukemia and carcinoma cell lines, elicited significant growth inhibitory and apoptotic synergis…
Epigenetic agents as an adjunct to active chemotherapy in hematological tumor cell lines
Epigenetic therapy is a new promising area in cancer research that is based on the use of a series of molecules capable of affecting tumor cell growth, differentiation and death by modifying the cellular mechanisms underlying the control of gene expression. Significant enhancement of traditional anticancer drug effects has been also reported by several authors. Our recent research focused on the identification of new epigenetic agent-containing drug combinations to be employed in the therapy of leukemia. The results showed that the new combination of an histone deacetylase (HDAC) inhibitor and the ribonucleotide reductase (RR) inhibitor 3’-methyl-adenosine (3’-Me-Ado) is endowed with a sign…
Effects of eztra virgin olive oil phenols on HL60 cell line sensitive and resistant to anthracycline.
Effects of extra virgin olive oil phenols on HL60 cell lines sensitive and resistant to anthracyclines
The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance). Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At …