78597-06-5Relevant academic research and scientific papers
Eco-friendly sequential one-pot synthesis, molecular docking, and anticancer evaluation of arylidene-hydrazinyl-thiazole derivatives as CDK2 inhibitors
El-Naggar, Abeer M.,El-Hashash, Maher A.,Elkaeed, Eslam B.
, (2021/02/05)
One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. CDK are a class of enzymes, which catalyze the transfer of the terminal phosphate of a molecule of ATP to a protein that acts
Synthesis, biological evaluation and quantitative structure-active relationships of 1,3-thiazolidin-4-one derivatives. A promising chemical scaffold endowed with high antifungal potency and low cytotoxicity
Carradori, Simone,Bizzarri, Bruna,D'Ascenzio, Melissa,De Monte, Celeste,Grande, Rossella,Rivanera, Daniela,Zicari, Alessanda,Mari, Emanuela,Sabatino, Manuela,Patsilinakos, Alexandros,Ragno, Rino,Secci, Daniela
, p. 274 - 292 (2017/10/05)
With reference to recent studies reporting on the various biological properties of the thiazolidinone scaffold, we synthesized more than a hundred compounds characterized by a 1,3-thiazolidin-4-one nucleus derivatised at the C2 with a hydrazine bridge linked to (cyclo)aliphatic or hetero(aryl) moieties, and their N-benzylated derivatives. These molecules were assayed as potential anti-Candida agents and they were shown to possess comparable, and in some cases higher biological activity than well-established topical and systemic antimycotic drugs (i.e. clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Compounds endowed with the lowest MICs underwent further testing in order to assess their cytotoxic effect (CC50) on Hep2 cells, which demonstrated their relative safety. Finally, QSAR and 3-D QSAR models were used to predict putative chemical modifications of the 1,3-thiazolidin-4-one scaffold in order to design new and potential more active compounds against Candida spp.
Anti-Candida activity and cytotoxicity of a large library of new N-substituted-1,3-thiazolidin-4-one derivatives
De Monte, Celeste,Carradori, Simone,Bizzarri, Bruna,Bolasco, Adriana,Caprara, Federica,Mollica, Adriano,Rivanera, Daniela,Mari, Emanuela,Zicari, Alessandra,Akdemir, Atilla,Secci, Daniela
, p. 82 - 96 (2015/11/18)
On the basis of the recent findings about the biological properties of thiazolidinones and taking into account the encouraging results about the antifungal activity of some (thiazol-2-yl)hydrazines, new N-substituted heterocyclic derivatives were designed combining the thiazolidinone nucleus with the hydrazonic portion. In details, 1,3-thiazolidin-4-ones bearing (cyclo)aliphatic or (hetero)aromatic moieties linked to the N1-hydrazine at C2 were synthesized and classified into three series according to the aromatic or bicyclic rings connected to the lactam nitrogen of the thiazolidinone. These molecules were assayed for their anti-Candida effects in reference to the biological activity of the conventional topic (clotrimazole, miconazole, tioconazole) and systemic drugs (fluconazole, ketoconazole, amphotericin B). Finally, we investigated the selectivity against fungal cells by testing the compounds endowed with the best MICs on Hep2 cells in order to assess their cell toxicity (CC50) and we noticed that two derivatives were less cytotoxic than the reference drug clotrimazole. Moreover, a preliminary molecular modelling approach has been performed against lanosterol 14-α demethylase (CYP51A1) to rationalize the activity of the tested compounds and to specify the target protein or enzyme.
Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma
De Monte, Celeste,Carradori, Simone,Secci, Daniela,D'Ascenzio, Melissa,Guglielmi, Paolo,Mollica, Adriano,Morrone, Stefania,Scarpa, Susanna,Aglianò, Anna Maria,Giantulli, Sabrina,Silvestri, Ida
, p. 245 - 262 (2015/11/03)
Antimitotic agents are widely used in cancer chemotherapy but the numerous side effects and the onset of resistance limit their clinical efficacy. Therefore, with the purpose of discovering more selective and efficient anticancer agents to be administered alone or in combination with traditional drugs, we synthesized a large library of 1,3,4-thiadiazoline analogues, maintaining the pharmacophoric structure of an antiproliferative compound known as K858: this is a new inhibitor of kinesin Eg5, able to induce the mitotic arrest in colorectal cancer cells and in xenograft ovarian cancer cells. We screened 103 compounds to assess their antiproliferative activity on PC3 prostate cancer cell line. Two derivatives, compounds 32 (corresponding to K858) and 33, have shown to be the most effective against prostate tumor cells and also towards two melanoma cell lines (SK-MEL-5 and SK-MEL-28) at low micromolar concentrations, confirming the pharmacological activity of this scaffold and revealing the potential role of 1,3,4-thiadiazolines in the management of cancer.
Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors
Secci, Daniela,Carradori, Simone,Bizzarri, Bruna,Bolasco, Adriana,Ballario, Paola,Patramani, Zoi,Fragapane, Paola,Vernarecci, Stefano,Canzonetta, Claudia,Filetici, Patrizia
, p. 1680 - 1689 (2014/03/21)
Acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation. Acetyltransferases are very well conserved through evolution. This allows the use of a simple model organism, such as budding yeast, for the study of their related processes and to discover specific inhibitors. Following a simple yeast-based chemogenetic approach, we have identified a novel HAT (histone acetyltransferase) inhibitor active both in vitro and in vivo. This new synthetic compound, 1-(4-(4-chlorophenyl)thiazol-2- yl)-2-(propan-2-ylidene)hydrazine, named BF1, showed substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HAT Gcn5 and p300. Finally, we tested BF1 on human cells, HeLa as control and two aggressive cancer cell lines: a neuroblastoma from neuronal tissue and glioblastoma from brain tumour. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) were lowered by BF1 treatment. Collectively, our results show the efficacy of this novel HAT inhibitor and propose the utilization of BF1 as a new, promising tool for future pharmacological studies.
Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: Enzyme and cellular studies
Carradori, Simone,Rotili, Dante,De Monte, Celeste,Lenoci, Alessia,D'Ascenzio, Melissa,Rodriguez, Veronica,Filetici, Patrizia,Miceli, Marco,Nebbioso, Angela,Altucci, Lucia,Secci, Daniela,Mai, Antonello
, p. 569 - 578 (2014/06/09)
Recently we described some (thiazol-2-yl)hydrazones as antiprotozoal, antifungal and anti-MAO agents as well as Gcn5 HAT inhibitors. Among these last compounds, CPTH2 and CPTH6 showed HAT inhibition in cells and broad anticancer properties. With the aim to identify HAT inhibitors more potent than the two prototypes, we synthesized several new (thiazol-2-yl)hydrazones including some related thiazolidines and pyrimidin-4(3H)-ones, and we tested the whole library existing in our lab against human p300 and PCAF HAT enzymes. Some compounds (1x, 1c', 1d', 1i' and 2m) were more efficient than CPTH2 and CPTH6 in inhibiting the p300 HAT enzyme. When tested in human leukemia U937 and colon carcinoma HCT116 cells (100 μM, 30 h), 1x, 1i' and 2m gave higher (U937 cells) or similar (HCT116 cells) apoptosis than CPTH6, and were more potent than CPTH6 in inducing cytodifferentiation (U937 cells).
Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii
D'Ascenzio, Melissa,Bizzarri, Bruna,De Monte, Celeste,Carradori, Simone,Bolasco, Adriana,Secci, Daniela,Rivanera, Daniela,Faulhaber, Nathan,Bordón, Claudia,Jones-Brando, Lorraine
, p. 17 - 30 (2014/09/16)
We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition.
Synthesis and selective human monoamine oxidase b inhibition of heterocyclic hybrids based on hydrazine and thiazole scaffolds
Carradori, Simone,D'Ascenzio, Melissa,De Monte, Celeste,Secci, Daniela,Yá?ez, Matilde
, p. 17 - 22 (2013/02/23)
A new scaffold of hydrazothiazoles has been designed as monoamine oxidase (MAO) inhibitors combining the hydrazine moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor (PPAR)γ agonists recently co-crystallized with human MAO-B. The resulting derivatives were synthesized and assayed to evaluate their in vitro activity against both the A and B isoforms of hMAO. All compounds were shown to be selective hMAO-B inhibitors with IC50 values in the low micromolar/high nanomolar range. Such results suggest that the hydrazothiazole scaffold could be considered as an interesting pharmacophore for the future design of new lead compounds as coadjuvants for the treatment of neurodegenerative diseases. The hydrazothiazole scaffold has been designed combining the hydrazide moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator-activated receptor γ agonists recently co-crystallized with human monoamine oxidase B (hMAO-B). The resulting derivatives were assayed to evaluate their in vitro inhibitory activity against both the A and B isoforms of hMAO. All compounds were shown to be selective and potent hMAO-B inhibitors in the low micromolar/high nanomolar range. Copyright
Synthesis, anti-Candida activity, and cytotoxicity of new (4-(4-iodophenyl)thiazol-2-yl)hydrazine derivatives
Secci, Daniela,Bizzarri, Bruna,Bolasco, Adriana,Carradori, Simone,D'Ascenzio, Melissa,Rivanera, Daniela,Mari, Emanuela,Polletta, Lucia,Zicari, Alessandra
experimental part, p. 246 - 253 (2012/08/28)
Novel (4-(4-iodophenyl)-thiazol-2-yl)hydrazine derivatives were assayed for their in vitro anti-Candida activity, compared to topical and systemic antifungal drugs, against twenty-seven clinical isolates. The presence of aliphatic chains or specific heteroaromatic rings on hydrazone moiety at position C2 and a 4-iodophenyl at C4 of the thiazole ring gave a promising inhibitory activity especially against Candida albicans and Candida krusei. The most active compounds have been also evaluated for their cytotoxicity and in association with clotrimazole for anti-Candida activity.
Recent advances in the development of selective human MAO-B inhibitors: (Hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines
Secci, Daniela,Bolasco, Adriana,Carradori, Simone,D'Ascenzio, Melissa,Nescatelli, Riccardo,Yá?ez, Matilde
, p. 405 - 417 (2013/02/21)
A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was synthesized in good yield and assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity. Most of them showed inhibitory activity in the nanomolar range and hMAO-B selective inhibition higher than reference drugs, demonstrating our interest in this privileged scaffold. The structure-activity relationship of the different rings on the N1-hydrazine position indicated that a pyridine ring was preferred with the presence of electron-withdrawing substituents on the aryl group at C4 of the thiazole nucleus. The substituent on the α-carbon to the N1-hydrazine moiety (methyl or hydrogen) had a great influence on the activity and hMAO-B selectivity. Moreover, the reversibility of the enzyme inhibition for the best active compound was reported.
