88419-01-6Relevant articles and documents
Design, Synthesis, and Biological Evaluation of a Series of Oxazolone Carboxamides as a Novel Class of Acid Ceramidase Inhibitors
Caputo, Samantha,Di Martino, Simona,Cilibrasi, Vincenzo,Tardia, Piero,Mazzonna, Marco,Russo, Debora,Penna, Ilaria,Summa, Maria,Bertozzi, Sine Mandrup,Realini, Natalia,Margaroli, Natasha,Migliore, Marco,Ottonello, Giuliana,Liu, Min,Lansbury, Peter,Armirotti, Andrea,Bertorelli, Rosalia,Ray, Soumya S.,Skerlj, Renato,Scarpelli, Rita
, p. 15821 - 15851 (2020/12/23)
Acid ceramidase (AC) is a cysteine hydrolase that plays a crucial role in the metabolism of lysosomal ceramides, important members of the sphingolipid family, a diversified class of bioactive molecules that mediate many biological processes ranging from cell structural integrity, signaling, and cell proliferation to cell death. In the effort to expand the structural diversity of the existing collection of AC inhibitors, a novel class of substituted oxazol-2-one-3-carboxamides were designed and synthesized. Herein, we present the chemical optimization of our initial hits, 2-oxo-4-phenyl-N-(4-phenylbutyl)oxazole-3-carboxamide 8a and 2-oxo-5-phenyl-N-(4-phenylbutyl)oxazole-3-carboxamide 12a, which resulted in the identification of 5-[4-fluoro-2-(1-methyl-4-piperidyl)phenyl]-2-oxo-N-pentyl-oxazole-3-carboxamide 32b as a potent AC inhibitor with optimal physicochemical and metabolic properties, showing target engagement in human neuroblastoma SH-SY5Y cells and a desirable pharmacokinetic profile in mice, following intravenous and oral administration. 32b enriches the arsenal of promising lead compounds that may therefore act as useful pharmacological tools for investigating the potential therapeutic effects of AC inhibition in relevant sphingolipid-mediated disorders.
Synthesis and in vitro cytotoxicity evaluation of β-carboline-linked 2,4-thiazolidinedione hybrids: potential DNA intercalation and apoptosis-inducing studies
Tokala, Ramya,Thatikonda, Sowjanya,Sana, Sravani,Regur, Phanindranath,Godugu, Chandraiah,Shankaraiah, Nagula
, p. 16226 - 16236 (2018/10/04)
A series of new β-carboline-thiazolidinedione hybrids was synthesized and assessed for in vitro cytotoxicity potential against selected human cancer cell lines, namely, PC-3, A549, MG-63, HCT-15, MDA-MB-231, A431, and PANC-1 along with a normal human cell line (L-132). Among this new series, compound 19e was found to exhibit promising cytotoxic effects against triple negative breast cancer cell line (MDA-MB-231) with IC50 value of 0.97 ± 0.13 μM. Hence, further mechanistic studies of the apoptosis-inducing effect of 19e were conducted on the MDA-MB-23 cell line. Moreover, characteristic apoptotic features such as membrane blebbing, chromatin condensation, and apoptotic body formation were observed with the effect of 19e on MDA-MB-231 cells using AO/EB and DAPI staining. The Annexin V-Alexa Flour 488/PI assay confirmed significant early apoptosis induction. Notably, DCFDA assay indicated that 19e induced ROS generation. Moreover, mitochondrial membrane potential collapse was observed through JC-1 staining by 19e. Furthermore, cell cycle analysis revealed that 19e arrested cells in the sub G1 phase. In addition, clonogenic and wound healing assays indicated inhibition of colony formation and cell migration by 19e in a dose-dependent manner. Next, molecular modelling and DNA binding affinity studies such as relative viscosity, circular dichroism and UV-visible spectroscopy denoted classic intercalation of 19e with CT-DNA with binding constant of 1 × 105 M?1.
Conventional and microwave-assisted synthesis of new 1H-benzimidazole-thiazolidinedione derivatives: A potential anticancer scaffold
Sharma, Pankaj,Reddy, T. Srinivasa,Kumar, Niggula Praveen,Senwar, Kishna Ram,Bhargava, Suresh K.,Shankaraiah, Nagula
, p. 234 - 245 (2017/07/04)
A series of new benzimidazole bearing thiazolidinedione derivatives has been designed, synthesized by using conventional as well as microwave-assisted methods. Microwave-assisted synthesis caused a significant reduction in the reaction times and improvement in the yields of all the derivatives. All the new synthesized compounds were evaluated for their in vitro cytotoxic potential against selected human cancer cell lines of breast (MDAMB-231), prostate (PC-3), cervical (HeLa), lung (A549) and bone (HT1080) along with a normal kidney cells (HeK-293T). The compounds 17n, 17p and 17q were found to be potent cytotoxic with IC50 values in the range of 0.096–0.63 μM on PC-3, HeLa, A549 and HT1080 cancer cells. Most of the compounds have found to be safe on normal HeK-293T kidney cells in comparison to cancer cells. The treatment of cells with 17p and 17q showed the typical apoptotic morphological features like fragmentation and shrinkage of nuclei. Further, test compounds resulted in inhibition of cell migration through disruption of F-actin protein assembly. Hoechst, DCFH-DA staining, mitochondrial membrane and annexin binding assays revealed that the cancer cell proliferation was inhibited through induction of apoptosis in A549 cells.
Studies on the synthetic and structural aspects of benzosuberones bearing 2, 4-thiazolidenone moiety as potential anti-cancer agents
Nagarapu, Lingaiah,Yadagiri, Bandi,Bantu, Rajashaker,Kumar, C. Ganesh,Pombala, Sujitha,Nanubolu, Jagadesh
, p. 91 - 97 (2014/01/06)
Novel representative of the important group of biologically active benzosuberones bearing 2, 4-thiazolidenone moiety was synthesized as potential anticancer agents (6a-j). These compounds were synthesized in good yields from Knoevenagel condensation of co
Synthesis and antidiabetic activity of morpholinothiazolyl-2,4- thiazolidindione derivatives
Ezer, Melis,Yildirim, Leyla Tatar,Bayro, Ornela,Verspohl, Eugen J.,Dundar, Oya Bozdag
scheme or table, p. 419 - 427 (2012/08/28)
We report the synthesis and the in vitro insulin releasing and glucose uptake activity of the morpholino thiazolyl-2,4-thiazolidinediones (1-15). Compounds 5, 1115 (at lower concentration; 0.001mg/ml) were able to increase insulin release in the presence
Synthesis and antimicrobial activity of some novel thiazolidine-2,4-dione derivatives
Mentese, Arzu,Ceylan-Uenluesoy, Meltem,Bozdag-Duendar, Oya,Altanlar, Nurten,Ertan, Rahmiye
scheme or table, p. 659 - 665 (2010/03/23)
In this study, a series of phenylethylsulfanyl-1,3-thiazolo-thiazolidine-2, 4-dione derivatives (VII a - f, VIIIa - f) and 5-methyl-[1,2,4]triazolyl- sulfanyl-1,3-thiazolo-thiazolidine-2,4-dione derivatives (IX a - f, Xa - f) were synthesized and evaluated for their antibacterial and antifungal activities against S. aureus (ATCC 25923), methicillin resistant S. aureus (MRSA ATCC 43300), B. subtilis (ATCC 6633), E. coli ( ATCC 23556) and C. albicans (ATCC10145). All the compounds were found active against used bacteria. ECV Editio Cantor Verlag.
Synthesis and pharmacological evaluation of some 3-phenacyl-5-benzylidene-thiazolidine-2,4-diones
De Lima,Perrissin,Chantegrel,Luu-Duc,Rousseau,Narcisse
, p. 831 - 834 (2007/10/02)
The synthesis of 54 3-phenacyl-5-benzylidene-thiazolidine-2,4-diones is reported. Eight of them were tested for anti-oedema, analgesic and anticonvulsant activity. Only one compound showed significant anti-oedematous and analgesic activity. Three compounds protected against tonic seizures and death.
RECYCLIZATION REACTIONS. RECYCLIZATIONS OF 3-ACYLMETHYL-2,4-THIAZOLIDINEDIONES BY THE ACTION OF NUCLEOPHILES
Shvaika, O. P.,Korotkikh, N. I.,Chervinskii, A. Yu.,Artemov, V. N.
, p. 1533 - 1543 (2007/10/02)
Four directions were established and investigated in the recyclization of 3-acylmethyl-2,4-thiazolidinediones with the participation of the side chain at the cyclic nitrogen atom and the formation of substituted 2-imidazolones or 2-oxazolones (under the influence of ammonia or hydroxides respectively), 2,5-diarylpyrazines (under the influence of methylamine), 6-monosubstituted or 2,6-disubstituted 4,5-dihydro-1,2,4-triazin-3-ones, and 5-substituted 1-amino-2-imidazolones (under the influence of hydrazine and phenylhydrazine).The directions of recyclization with hydrazines are determined by the stereochemical configuration of the intermediate hydrazones; the E-hydrazones of 3-acylmethyl-2,4-thiazolidenediones are converted into 4,5-dihydro-1,2,4-triazin-3-ones, while the Z izomers are converted into 1-amino-2-imidazolones.
