RESUMO
Rhein is used as an active ingredient in laxatives in medicinal herbal products and is a chemical marker for quality control purposes. Thus, a simple and effective method for the optimized extraction of a high amount of rhein from the fruit pulp of Cassia fistula was investigated using ultrasonic-assisted extraction (UAE). The response surface methodology was applied to find the most suitable parameters for optimizing the extraction process and to study the factors' relationships with each other. The best conditions for ultrasonic extraction were the application of 1:40 g/mL solid-to-liquid ratio and 10% EtOH-H2O as a solvent at 75 °C for 40 min. This method was compared to a conventional decoction in two variations. In these experiments, it was confirmed that the UAE was more favorable than the decoction methods. The resulting crude extract was further purified by liquid-liquid extraction with a basic pH adjustment, followed by recrystallization. High-purity rhein was obtained by using chromatographic techniques and nuclear magnetic resonance spectroscopy. Therefore, this study suggests that UAE is an efficient alternative method for the extraction of rhein from C. fistula pod pulp. The resulting optimized conditions can be applied as a useful tool for the large-scale industrial production of a rhein-rich plant extract.
Assuntos
Antraquinonas/química , Cassia/química , Ultrassom , Fracionamento Químico , Frutas/química , Extratos Vegetais/química , Plantas Medicinais/químicaRESUMO
Azanaphthoquinone annelated pyrrole derivatives have been developed and synthesized with a continuous attempt to develop novel DNA intercalating agents as anti-cancer compounds with lower organ toxicity. With the remarkable antiproliferative activity of synthesized azanaphthoquinone annelated pyrrole derivatives, a structurally novel scaffold of these compounds is appropriated for further development of novel anti-cancer agents. Therefore, in the present study, 3D QSAR study (CoMSIA) was applied on 28 azanaphthoquinone annelated pyrrole derivatives to evaluate the structural requirement of these compounds. The resulting CoMSIA model is satisfied with r(2) of 0.99 and q(2) of 0.65. The interpretation of CoMSIA contours reveals the significant importance of steric, electrostatic, hydrophobic and hydrogen acceptor descriptors on the activities of azanaphthoquinone annelated pyrrole derivatives. Remarkably, the structural requirement of six substituent positions on the azanaphthoquinone annelated pyrrole scaffold was elucidated here. This result is the useful concept for design of new and more active azanaphthoquinone annelated pyrrole derivatives. Moreover, MD simulations using AMBER program were performed to model the binding of azanaphthoquinone annelated pyrrole derivatives in the intercalation site of the DNA duplex. Based on MD simulations, the information in terms of ligand-DNA interaction, complex structure and binding free energy was provided in this work. Therefore, the integrated results are informative for further modification of azanaphthoquinone annelated pyrrole scaffold leading to gain novel azanaphthoquinone annelated pyrrole derivatives possessing better antiproliferative activity.
RESUMO
Two series of azanaphthoquinone annelated pyrrolo oximes have been synthesized. The antiproliferative activities of 10 compounds were evaluated on at least four different cell lines. One series of pyrrolo derivatives showed high cytotoxic activity. The effects on cell cycle and caspase activity were investigated. Compounds 9a and 9b showed an accumulation of cells in G2/M phase. Substantial and dose-dependent caspase activity was found after treatment of cells with 9a and 9b. This indicates an apoptosis inducing property of these compounds.