RESUMEN
Spirooxindoles occupy an important place in heterocyclic chemistry. Many natural spirooxindole-containing compounds have been identified as bio-promising agents. Synthetic analogs have also been synthesized utilizing different pathways. The present article summarizes the recent development of both natural and synthetic spirooxindole-containing compounds prepared from isatin or its derivatives reported in the last five years. The spirooxindoles are categorized based on their mentioned biological properties.
Asunto(s)
Isatina , Compuestos de Espiro , Indoles/química , Compuestos de Espiro/farmacología , Compuestos de Espiro/química , Isatina/farmacología , Isatina/químicaRESUMEN
Azomethine ylides are nitrogen-based three-atom components commonly used in [3+2]-cycloaddition reactions with various unsaturated 2π-electron components. These reactions are highly regio- and stereoselective and have attracted the attention of organic chemists with respect to the construction of diverse heterocycles potentially bearing four new contiguous stereogenic centers. This review article complies the most important [3+2]-cycloaddition reactions of azomethine ylides with various olefinic, unsaturated 2π-electron components (acyclic, alicyclic, heterocyclic, and exocyclic ones) reported over the past two decades.
RESUMEN
The discovery of a new class of extracellular-signal-regulated kinase (ERK) inhibitors has been achieved via developing novel 2-imino-5-arylidene-thiazolidine analogues. A novel synthetic method employing a solid support-mediated reaction was used to construct the targeted thiazolidines through a cascade reaction with good yields. The chemical and physical stability of the new thiazolidine library has successfully been achieved by blocking the labile C5-position to aerobic oxidation. A cell viability study was performed using esophageal squamous cell carcinoma cell lines (KYSE-30 and KYSE-150) and non-tumorous esophageal epithelial cell lines (HET-1A and NES-G4T) through utilization of an MTT assay, revealing that (Z)-5-((Z)-4-bromobenzylidene)-N-(4-methoxy-2-nitrophenyl)-4,4-dimethylthiazolidin-2-imine (6g) was the best compound among the synthesized library in terms of selectivity. DAPI staining experiments were performed to visualize the morphological changes and to investigate the apoptotic activity. Moreover, western blots were used to probe the mechanism/pathway behind the observed activity/selectivity of thiazolidine 6g which established selective inhibition of phosphorylation in the ERK pathway. Molecular modeling techniques have been utilized to confirm the observed activity. A molecular docking study revealed similar binding interactions between the synthesized thiazolidines and reported co-crystalized inhibitors with ERK proteins. Thus, the present study provides a starting point for the development of interesting bioactive 2-imino-5-arylidene-thiazolidines.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Tiazolidinas/farmacología , Tiazolidinas/química , Neoplasias Esofágicas/patología , Sistema de Señalización de MAP Quinasas , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Proliferación CelularRESUMEN
An efficient surface-mediated synthetic method to facilitate access to a novel class of thiazolidines is described. The rationale behind the design of the targeted thiazolidines was to prepare stable thiazolidine analogues and evaluate their anti-proliferative activity against a breast cancer cell line (MCF7). Most of the synthesized analogues exhibited increased potency ranging from 2-15-fold higher compared to the standard reference, cisplatin. The most active thiazolidines contain a halogenated or electron withdrawing group attached to the N-phenyl ring of exocyclic 2-imino group. However, combination of the two substituents did not enhance the activity. The anti-proliferative activity was measured in terms of IC50 values using an MTT assay.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Tiazolidinas , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Células MCF-7 , Relación Estructura-Actividad , Tiazolidinas/síntesis química , Tiazolidinas/química , Tiazolidinas/farmacologíaRESUMEN
A series of N-substituted (Z)-2-imino-(5Z)-ylidene thiazolidines/thiazolidin-4-ones were synthesized and their antiproliferative activities against colon (HCT-116) and breast (MCF7) cancer cell lines were evaluated utilizing an MTT growth assay. A 2D-QSAR investigation was conducted to probe and validate the obtained antiproliferative properties for the thiazolidine derivatives. The majority of the thiazolidines exhibit higher potency against a colon cancer cell line relative to the standard reference. The p-halophenylimino p-anisylidene derivatives exhibited the highest anti-proliferative activity against HCT116 relative to control (IC50â¯=â¯8.9-10.0⯵M compared to 20.4⯵M observed for 5-fluorouracil as positive control). An X-ray study confirmed the Z, Z'-configurations for two examples of the synthesized compounds.
Asunto(s)
Antineoplásicos/farmacología , Relación Estructura-Actividad Cuantitativa , Tiazolidinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Células MCF-7 , Modelos Moleculares , Estructura Molecular , Tiazolidinas/síntesis química , Tiazolidinas/químicaRESUMEN
A Facile synthetic approach is reported towards 4-hydroxyquinazoline-4-carboxamides 13a-i through ring expansion of 2,3-dioxoindoline-1-carboxamides 10a-c during secondary amine 11a-d nucleophilic reaction. Single crystal X-ray studies of 10c and 13d support the structures. Some of the synthesized quinazolinecarboxamides 13 show promising vasorelaxant properties with potency higher than that of Doxazosin through the pre-contracted (norepinephrine hydrochloride) rat aorta standard bioassay. Good molecular models (2D-QSAR, pharmacophore) describe the biological observations.
RESUMEN
Facile synthetic pathway for nicotinonitriles 5aâo, 7aâi was demonstrated through reaction of ketones 4aâk, 6aâf with ylidenemalononitrile 3 in the presence of sodium alkoxide. Meanwhile, nucleophilic attack of amines on 2-bromonicotinonitrile 9 (obtained through reaction of propenone 8 with malononitrile, followed by bromination with bromine in acetic acid) afforded 3-pyridinecarbonitriles 11aâd. Single crystal X-ray of compound 7i reveals the monoclinic space group C2/c with 8 molecules per unit cell. Optimized structure of 7i [DFT/B3LYP, 6-31G(d,p)] shows close correlations to that of X-ray study. Compound 5l seems superior among all the synthesized analogues exhibiting bronchodilation properties about three folds potency compared to theophylline (standard reference) through pre-contracted tracheal rings with histamine standard method. Also compound 5a reveals promising observations (about two folds potency of the standard reference). Molecular modeling studies (3D-pharmacophore and 2D-QSAR) supported the observed biological properties.