RESUMEN
Osteoporosis is a disease that affects the quality of life of elderly people. The balance between bone formation mediated by osteoblasts and bone resorption by osteoclasts is important to maintain the normal bone condition. Therefore, the promotion of osteoblast differentiation and the suppression of osteoclastogenesis are effective strategies for osteoporosis treatment. Marine organisms are a promising source of biologically active and structurally diverse secondary metabolites, and have been providing drug leads for the treatment of numerous diseases. We describe the marine-derived secondary metabolites that can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and promote osteoblast differentiation.
Asunto(s)
Productos Biológicos , Osteoporosis , Anciano , Productos Biológicos/metabolismo , Productos Biológicos/farmacología , Diferenciación Celular , Humanos , Osteoblastos , Osteogénesis , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Calidad de VidaRESUMEN
Three new diterpenes, stellejasmins A (1) and B (2) and 12-O-benzoylphorbol-13-heptanoate (3), were isolated from the roots of Stellera chamaejasme L. The structures of 1-3 were elucidated by extensive NMR and mass spectroscopic analyses. Compounds 1 and 2 are the first derivatives containing a hydroxy group at C-2 in the family of daphnane and tigliane diterpenes. The presence of a chlorine atom in 1 is unique in the plant metabolite. Compound 3 has an odd-number acyl group, which is biosynthetically notable. Human immunodeficiency virus (HIV) LTR-driven transcription activity was tested with 1-3 and 17 known diterpenes isolated from S. chamaejasme L. and Wikstroemia retusa A.Gray. Among these, gnidimacrin (4), stelleralide A (5), and wikstroelide A (20) were highly potent, with EC50 values of 0.14, 0.33, and 0.39 nM, respectively. The structure-activity relationship (SAR) was investigated using 20 natural and eight synthetic diterpenes. This is the first SAR study on natural daphnane and tigliane diterpenes.
Asunto(s)
Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacología , Diterpenos/síntesis química , Diterpenos/farmacología , VIH/efectos de los fármacos , Forboles/química , Latencia del Virus/efectos de los fármacos , Diterpenos/química , Modelos Moleculares , Simulación del Acoplamiento Molecular , Forboles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Relación Estructura-Actividad , Thymelaeaceae/química , Wikstroemia/químicaRESUMEN
Four new guaiane-type sesquiterpenes, chamaejasmins A-D (1-4), were isolated from the root of Stellera camaejasme L. collected in Nepal, together with two known terpenes, stelleraguaianone B (5) and 1α,7α,10αH-guaia-4,11-dien-3-one (6). The structures of 1-4 including their absolute configurations were determined by extensive 2D NMR analyses, mass spectroscopy, and TDDFT calculations of their 13C chemical shifts and ECD spectra. Chamaejasmin A (1) showed cytotoxicity against HeLa cells with an IC50 value of 6.3 µM.