RESUMEN
A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC(50) values of 0.3 and 0.5 µM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 µM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI(50) values ranging from 0.70 to 13.10 µM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling.
Asunto(s)
Antineoplásicos/química , Apoptosis , Chalconas/química , Piridinas/química , Factor de Transcripción ReIA/antagonistas & inhibidores , Receptor fas/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Chalconas/síntesis química , Chalconas/toxicidad , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Piridinas/síntesis química , Piridinas/toxicidad , Factor de Transcripción ReIA/metabolismoRESUMEN
Some chalcones exert potent anti-inflammatory activities. Mannich bases of heterocyclic chalcones inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-γ stimulated RAW 264.7 macrophages. Also Formyl-Met-Leu-Phe and cytochalasin B induced superoxide anion generation (O2·-) and elastase release in human neutrophils. Mannich bases of heterocyclic chalcone analogs exhibited potent inhibitory effects on NO production with IC(50) values ranges between 10.5 and 0.018 µM, O2·- generation (IC(50) 39.87-0.68 µM) and elastase release (IC(50) 39.74-0.95 µM). Compound 29 (IC(50) 0.055 µM) and 34 (IC(50) 0.018 µM) were showed excellent inhibition on NO production. On the other hand, compounds 2 and 8 showed potent inhibition on O2·- generation and elastase release. Therefore, these four compounds may be new leads for development of anti-inflammatory activities. The structure-activity relationships are also discussed.
Asunto(s)
Chalconas/farmacología , Macrófagos/metabolismo , Neutrófilos/metabolismo , Óxido Nítrico/biosíntesis , Elastasa Pancreática/metabolismo , Superóxidos/metabolismo , Animales , Antiinflamatorios , Chalconas/química , Compuestos Heterocíclicos , Humanos , Activación de Macrófagos , Ratones , Relación Estructura-ActividadRESUMEN
The chalcone skeleton (1,3-diphenyl-2-propen-1-one) is a unique template that is associated with various biological activities. We synthesized Mannich bases of heterocyclic chalcones (9-47) using a one-step Claisen-Schmidt condensation of heterocyclic aldehydes with Mannich bases of acetophenones, and tested the target compounds for cytotoxicity against three human cancer cell lines (prostate, PC-3; breast, MCF-7; nasopharynx, KB) and a multi-drug resistant subline (KB-VIN). Out of the 39 chalcones synthesized, 31 compounds showed potent activity against at least one cell line with IC(50) values ranging from 0.03 to 3.80 microg/mL. Structure-activity relationships (SAR) are also discussed.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Chalconas/química , Chalconas/farmacología , Línea Celular Tumoral , Diseño de Fármacos , Humanos , Bases de Mannich , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A new naphthoquinone, 2,7-dihydroxy-8-formyl-5-isopropyl-3-methyl-1,4-naphthoquinone (1) together with a known naphthoquinone, 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (2), has been isolated from the heartwood of Ceiba pentandra. The structures of 1 and 2 have been elucidated by extensive 1D and 2D NMR experiments.
Asunto(s)
Ceiba/química , Naftoquinonas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Naftoquinonas/químicaRESUMEN
Three flavonoids, 5,7,2',3',4'-pentamethoxyflavone (1), 2'-hydroxy-2,4',6'-tri methoxychalcone (2) and dihydroskullcapflavone I (3), together with 17,19,20-trihydroxy-5beta, 8alpha H, 9beta H,10alpha-labd-13-en-16,15-olactone (4), a known diterpenoid and six known flavonoids, 5-hydroxy-7,8-dimethoxyflavanone (5), 5-hydroxy-7,8,2',3',4'-pentamethoxyflavone (6), 5,2'-dihydroxy-7-methoxyflavanone (7), 5,2'-dihydroxy-7,8-dimethoxyflavone (8), 5,2'-dihydroxy-7-methoxyflavone (9) and 5,2'-dihydroxy-7-methoxyflavone 2'-O-beta-D-glucopyranoside (10) were isolated from the whole plant of Andrographis lineata. The structures of these compounds were elucidated on the basis of spectral and chemical studies.