Diseño, síntesis y estudio de acoplamiento molecular de híbridos de quinazolinona- tiazolidin-4-onas como agentes anticancerígenos

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4-fluorophenyl)-4-oxo-5- (arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4- fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin-3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035±0.002 μM, 0.031±0.002 μM and 0.030±0.002 μM respectively compared to 0.023±0.002 μM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 - 0.050 μM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed.Una serie de 2- (4-sustituido fenil) -4-oxoquinazolin-3 (4H) -il) -N- (2- (4-fluorofenil) -4-oxo-5- (arilideno) tiazolidin-3-ilo) benzamidas (VIa-n) han sido sintetizadas por condensación de N- (2- (4-fluorofenil) -4-oxotiazolidin-3-il) -4- (4-oxo-2- (4-fenil sustituido) quinazolin-3 (4H) -il) benzamidas (Va-b) con diversos aldehídos de arilo / heteroarilo usando metodología convencional. Todos los compuestos se cribaron para su actividad anticancerosa in vitro contra las líneas celulares de cáncer de mama humano (MCF-7), líneas celulares de cáncer de pulmón humano (A549) usando el método de ensayo MTT y se usa doxorrubicina como fármaco estándar. El compuesto VId, VIk y VIn mostraron alta potencia contra las líneas celulares A549 con valores IC50 de 0.035 ± 0.002 μM, 0.031 ± 0.002 μM y 0.030 ± 0.002 μM, respectivamente, en comparación con 0.023 ± 0.002 μM mostrada por el estándar. Sin embargo, la actividad más alta contra líneas celulares MCF-7 fue exhibida por Va, Vb, VIk y VIn con valores de CI50 entre 0.040 - 0.050 μM. Todos los compuestos restantes mostraron una actividad anticancerígena moderada contra las líneas celulares MCF-7 y A549. Para comprender las interacciones con el sitio de unión activa del receptor, también se realizó el estudio de acoplamiento molecular

Synthesis and Evaluation of New Series of 1,4-Dihydropyridine Derivatives as Anticancer Agents

1,4-dihydropyridine derivatives represent one of the important classes of compounds possessing a wide variety of biological activities including anticancer activity. In the present study, (4-Alkyl/Aryl-1-substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxilicacid, 3,5-bis [2(aminothioxomethyl)hydrazides]) (6 a-l) were synthesized by the reaction of 4-alkyl/aryl-3,5-dicarboalkoxy-2,6-dimethyl-1,4-dihydropyridines (4 a-l) with thisemicarbazide and evaluated for their anti-cancer properties. All the synthesized compounds were characterized by IR, NMR and Mass spectra and were screened to evaluating for anticancer activity against three cell lines (MCF-7, HeLa and Hep G2) by using MTT assay method. The results showed that compounds 6j and 6l showed significant cytotoxicity with IC50 values ranging from 5

Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: synthesis and SAR studies

Mitogen activated protein kinases including c-Jun N-terminal kinase play an indispensable role in inflammatory diseases. Investigation of reported JNK-1 inhibitors indicated that diverse heterocyclic compounds bearing an amide group rendered potent JNK-1 inhibitory activity which prompted us to synthesize new JNK-1 inhibitors containing a pyrazole heterocyclic group. A DABCO mediated 1,3-dipolar cycloaddition reaction in neat resulted in pyrazole carboxylic acid which was converted to desired amides. Upon confirmation of the structures, all the compounds were screened for JNK-1 inhibitory activity and in vivo anti-inflammatory activity. Several synthesized analogues have exhibited JNK-1 inhibitory activity less than 10 μM, in particular compounds 9c, 10a and 10d were found to be potent among all the compounds