RESUMEN
In continuation of studies for α-MSH stimulated melanogenesis inhibitors, we have evaluated the design, synthesis, and activity of a new series of chlorogenic acid (CGA) analogues comprising pyridine, pyrimidine, and diacyl derivatives. Among nineteen synthesized compounds, most of them (fifteen) exhibited better inhibitions of melanin formation in B16 melanoma cells. The results illustrated that a pyridine analogue 6f and a diacyl derivative 13a of CGA showed superior inhibition profiles (IC50: 2.5 ± 0.7 µM and 1.1 ± 0.1 µM, respectively) of α-MSH activities than positive controls, kojic acid and arbutin (IC50: 54 ± 1.5 µM and 380 ± 9.5 µM, respectively). The SAR studies showed that both -CF3 and -Cl groups exhibited better inhibition at the meta position on benzylamine than their ortho and para positions. In addition, the stability of diacyl analogues of CGA in methanol monitored by HPLC for 28 days indicated the steric bulkiness of acyl substituents as a key factor in their stability.
RESUMEN
For the systematic SAR study on mansonone F, a series of C6 and C9 analogs of mansonone F have been synthesized and their anti-MRSA activities were evaluated. Most of the analogs exhibited good or excellent anti-MRSA activities. In particular, the 6-n-butylmansonone F showed fourfold higher antibacterial activities compared to that of vancomycin.
Asunto(s)
Naftoquinonas/química , Quinonas/química , Sesquiterpenos/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana , Meticilina/farmacología , Modelos Químicos , Naftoquinonas/metabolismo , Sesquiterpenos/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/metabolismo , Relación Estructura-Actividad , Vancomicina/químicaRESUMEN
Syntheses and excellent anti-MRSA activities of the mansonone F analogs are reported. In addition, the minimal structural requirements for its anti-MRSA activities as well as its structure-activity relationship including the C3 substituents effects on anti-MRSA activity are also described. In particular, this study revealed that both ortho-quinone and tricyclic systems of mansonone F are essential for anti-MRSA activities.