Validation of a spectrophotometric method for quantification of xanthone in biodegradable nanoparticles

Xanthone has been incorporated for the first time in nanoparticles of poly(D,L-lactide-co-glycolide) (PLGA). For this purpose the estimation of xanthone content in the nanoparticles is a crucial tool for guaranteeing the reliability of the results. Thus, a simple spectrophotometric method was validated according to USP25 and ICH guidelines for its specificity, linearity, accuracy and precision. The method was found to be specific for xanthone in the presence of nanoparticle excipients. The calibration curve was linear over the concentration range of 0.5 to 4.0 mug/mL (r > 0.999). Recovery of xanthone from nanoparticles ranged from 86.5 to 95.9%. Repeatability (intra-assay precision) and intermediate precision were found to be acceptable with relative standard deviations values (RSD) ranging from 0.3 to 3.0% and from 1.4 to 3.1%, respectively. The method was found to be suitable for the evaluation of xanthone content in nanoparticles of PLGA

Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone

The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter 77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN

Determination of the absolute configuration of bioactive indole-containing pyrazino[2,1-b]quinazoline-3,6-diones and study of their in vitro metabolic profile

In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyra-zino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respec-tively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (- )-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. In vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.This research was supported by national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF) and COMPETE under the Strategic Funding of CIIMAR UIDB/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) and LAQV-REQUIMTE (UIDB/50006/2020) and the project PTDC/SAU-PUB/28736/2017 (Reference: POCI-01–0145-FEDER-028736), as well as CHIRALBIOACTIVE-PI-3RL-IINFACTS-2019. This work is also a result of the project ATLANTIDA (Reference: NORTE-01-0145-FEDER-000040), supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement and through the European Regional Development Fund (ERDF). Additionally, this research was supported by the Agency for the Improvement of Higher Education Personnel (CAPES) (Finance Code 001), National Council for Scientific and Technological Development (CNPq) (Grant Number 406064/2018-05), São Paulo Research Foundation (FAPESP) (Grant Number: 2020/05965-8 and Ph.D. scholarships 2018/03035-3 and 2019/15040-4)

Effect of abietane diterpenes from Plectranthus grandidentatus on the growth of human cancer cell lines

Five known abietane diterpenes, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4), and coleon U (5), isolated from Plectranthus grandidentatus Gurke, were evaluated for their in vitro anti proliferative activity against five human cancer cell lines MCF-7, NCI-H460, SF-268, TK-10, and UACC-62. Coleon U (5) exhibited the strongest effect among all the assayed compounds. The abietane 3 revealed also a strong inhibitory effect while diterpenes 2 and 4 inhibited only slightly the growth of all cancer cell lines

Development and validation of an HPLC method for the quantification of a cytotoxic dihydropyranoxanthone in biodegradable nanoparticles

Context and purpose 3,4-dihydro-12-hydroxy-2,2-dimethyl-2H(6Hi-pyrano[3,2-b]xanthen-6-one (compound 1) is a cytotoxic dihydropyranoxanthone exhibiting antiproliferative effects, inducing S-phase cell cycle arrest, and increasing the percentage of apoptotic cells in leukemia cell lines. Nevertheless, the poor aqueous solubility of compound 1 is a major drawback not only for its potential use in therapy but even for the in vitro assessment of its biological activity. Polymeric nanoparticles formulations were developed as potential carriers to overcome problems related with low water solubility of compound 1. The objective of this work was to develop and validate a specific, sensitive and simple HPLC method for the quantitative analysis of the prenylated xanthone (compound 1), which was entrapped in PLGA nanoparticles for the first time. Main findings Chromatographic separation was performed with a reversed-phase C18 column, using methanol: water (85:15, v/v) containing 1 % (v/v) acetic acid as a mobile phase at a flow rate of 1 ml/min and quantification was made by UV detection at 254 nm. The isocratic system required 10 minutes of chromatographic run. The method was shown to be linear (r> 0.999) over the concentration range of 0.50-3.00 pg/ml and precise at the intra-day and inter-day levels as reflected by the relative standard deviation values (lower than 1.5% and 1.6%, respectively). The mean recovery ranged from 97.53 to 104.28 % (RSD: 0.027%) and from 98.49 to 101.81% (RSD: 0.019 %) for nanospheres and nanocapsules, respectively. Brief summary and potential implications A simple, linear, sensitive, accurate, and precise HPLC method suitable for the quantification of compound 1 incorporated in polymeric nanoparticles was developed and validated

Effect of abietane diterpenes from Plectranthus grandidentatus on T- and B-lymphocyte proliferation

Five known abietane diterpenes of the royleanone and coleon type, namely, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4) and coleon U (5), isolated from Plectranthus grandidentatus, were evaluated for their effect on the proliferation of human lymphocytes induced by the mitogen PHA. All except 4, showed a dose-dependent suppressor effect, with 3 yielding the most potent antiproliferative activity, followed by 5. These two compounds, that represent diterpenes of the royleanone and coleon type respectively, were also shown to be potent inhibitors of mouse splenocyte proliferation induced by ConA or LPS mitogens. However, the sensitivity of ConA-stimulated splenocytes to their suppressive effect was higher, suggesting a preferential inhibition of T-lymphocyte proliferation. The antiproliferative activity of 3 seemed to be exerted without affecting the expression of the lymphocyte activation marker CD69. On the contrary, 5 was shown to reduce the expression of CD69 of TCD8(+) and B-cells, suggesting a relationship between its antiproliferative effect and the expression of this early marker of activation on these cell populations. The capacity of 5 to induce apoptosis on ConA-stimulated splenocytes could also be related with its antiproliferative activity. (C) 2003 Elsevier Ltd. All rights reserved