Evaluation of a Series of 9,10-Anthraquinones as Antiplasmodial Agents

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. Objective: The present study aimed to investigate the structural requirements of 9,10- anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 µM, and when C-6 was substituted with a methyl group, 1,3- dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02 µM, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 Å and 3.02 Å, respectively. Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin

Analysis of Students’ Cognitive Presence and Perception in a Custom-Designed Virtual Problem Based Learning Assignment

All the teaching and learning activities except laboratory-based practicals remained conducted virtually during the transition from the Covid-19 pandemic to the endemic phase. The problem-based assignment for Pharmaceutical Analysis was conducted virtually.  This study aims to evaluate students’ level of engagement and perception of virtual engagement to complete an online problem-based assignment on real situations using the cooperative Jigsaw model. Jamboard was used as an online communication tool to connect the students and facilitators. The content of the written discussion posted on the Jamboard and the questionnaire survey were analysed to establish the level of engagement. The student’s perception of virtual engagement was based on a questionnaire survey using descriptive analysis.  Analysis of the student’s opinion posted on the Jamboard showed the presence of cognitive, social, and teaching components in the level of engagement during the virtual discussion.  The information from the internet is borderless and the facilitators need to be knowledgeable to explain, guide, and stimulate higher-order thinking among the students. With careful course design, the Jigsaw cooperative activity on real problem-based questions could use to facilitate collaborative problem-solving skills among the students

Analysis of Sterol Glucosides in Momordica charantia L. Extracts and Nutraceutical Products: Analysis of Sterol Glucosides

Sterol glucosides were biosynthesised in Momordica charantia L. and used as markers for the standardization of M. charantia extracts. The sterol glucoside, charantin, used as a marker consisted of equal amounts of two sterol glucosides, namely, 5, 25-stigmastadienol glucoside (1) and β-sitosterol glucoside (2). Most quantitation methods either mixed up both isomers, namely (1) and stigmasterol glucoside (3) or both the sterol glucosides (1) and (2) were not separated in the quantitation methods. The labelling of individual sterol glucosides needs to be clearly stated in nutraceutical products. This study aimed to resolve the separation of the commonly mixed-up sterol glucosides and further validate a high-performance liquid chromatography-photodiode array detector (HPLC-PDA) method for the quantification of individual sterol glucosides in M. charantia. The HPLC-PDA instrument was used for method development as it is a universal instrument available in most nutraceutical companies. Sterol glucosides (1)-(3) were separated with a Zorbax SB-C18 column and an isocratic HPLC mobile phase system of 88% methanol in deionized water. The wavelength of the PDA detector was set at 200 to 500 nm with a linearity range of 90 to 300 μg/mL and a good correlation coefficient of r2 > 0.99. The validated method was applied to fresh fruits and nutraceutical products. The sterol glucoside (1) is the major constituent in charantin. Hybrid fruits biosynthesised higher content of sterol glucosides compared to non-hybrid fruits. The content of (1)-(3) in the final nutraceutical products fluctuates and dependent on the source of raw material. Thus, standardization of extracts is essential in nutraceutical production to ensure uniform content of secondary metabolites and reproducible therapeutic effect

Living losses in stroke caregiving: a qualitative systematic review of systematic reviews on psycho-socio-emotional challenges and coping mechanisms

Stroke compromises the quality of life and wellbeing of stroke survivors and families as a whole. The unexpected caregiving responsibilities often cause psychological distress, overwhelming emotions, living losses and grief, and relational conflicts with stroke survivors. Despite the increasing research to better understand their needs, empirically sound and holistic psychosocial interventions for stroke caregivers are lacking.This study is part of a larger project funded by Rehabilitation Research Institute of Singapore, Third Rehabilitation Research Grant (RRG3) (reference no.: RRG3/19004). The funder has played no role in study design, analysis and interpretation of data, or preparation of articles

Evaluation of Rennellia Elliptica as Potential Antiplasmodial Herbal Remedy

Rennellia elliptica (Rubiaceae) has been used by local Jakun Community in the Endau Rompin State Park for the treatment of jaundice. Previous study has revealed the antiplasmodial activity of the root extract and major anthraquinones isolated from the roots. The present study entails the optimization of extraction methods, qualitative and quantitative analyses of selected marker anthraquinones and in vivo antiplasmodial activity along with toxicity and inhibition of β-hematin in vitro. HPLC profile showed the present of marker compounds as major constituents with content ranging 3-12 µg/g extract. The root extract showed potent antiplasmodial activity against rodent malaria, Plasmodium berghei with ED50 value of 1.23 µg/ml BW. The major anthraquinones, damnacanthal and nordamnacanthal showed significant inhibition against β-hematin formation via lipids and HRP2 catalyses. However, the root extract is slightly toxic against hepatocyte cell. These data suggests that R. elliptica is a potential herbal remedy for malaria treatment and antiplasmodial of the root extract possibly due to the action of major anthraquinones

Eurycomanone and Eurycomanol from Eurycoma longifolia Jack as Regulators of Signaling Pathways Involved in Proliferation, Cell Death and Inflammation

Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,β-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition

Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples

10.1136/jclinpath-2011-200009Journal of Clinical Pathology6410880-883JCPA