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Objectives: The rapid spread of antimalarial drug resistance is becoming a problem in the treatment of malaria. The fact was indicated the importance of finding new antimalarial drugs. The genus Garcinia is well known to be a rich source of bioactive prenylated xanthones and triterpenes reported for their antimalarial activity. is one of the Garcinia genera that can be explored for the search of new antimalarial drugs. This study was aimed to determine the antimalarial activities of extracts and fractions.
Methods: Miq. stem was collected from Balikpapan Botanical Garden in East Kalimantan, Indonesia, was extracted gradually with n-hexane, dichloromethane, and methanol by ultrasonic assisted method. The most active extract was further separated using the open column chromatography method. All extracts and fractions were tested against 3D7 using lactate dehydrogenase (LDH) assay and followed by IC determination.
Results: The results showed that all extracts inhibit growth by LDH assay. The highest inhibition was showed by dichloromethane stem extract (BP12-S-D) with the IC value of 6.61 ± 0.09 μg/mL. Further fractionation of BP12-S-D has obtained 10 fractions. All of them were identified by TLC, and a brownish-yellow spot (fraction-1) appears after spraying with 10% HSO. Fraction-1 (F1) performed the highest parasite growth inhibition with the IC value of 6.00 ± 0.03 μg/mL compared with other fractions. This fraction was classified as having a promising activity of antimalarial. The fraction-1 was identified using HPLC, and two major peaks were observed (A and B). The UV-Vis spectra showed the absorption at wavelengths 250 and 278 (A), 243, 281, and 317 nm (B). Based on the profile of TLC, HPLC, and UV-Vis spectra of F1, it was expected that the active compounds are flavonoid (A) and xanthone (B).
Conclusions: The fraction-1 of dichloromethane extract of Miq. stem has the highest antimalarial activity. It might be a potential candidate for the new antimalarial drug.
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http://dx.doi.org/10.1515/jbcpp-2020-0414 | DOI Listing |
Lupus Sci Med
December 2024
Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
Objective: To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA.
Methods: Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period.
Cancer Med
December 2024
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, People's Republic of China.
Background: Methylthioadenosine phosphorylase (MTAP) and protein arginine methyltransferase 5 (PRMT5) are considered to be a synthetic lethal pair of targets, due to the fact that deletion of MTAP leads to massive production of methylthioadenosine (MTA) decreasing the activity of PRMT5. In vitro and in vivo experiments have demonstrated that MRTX1719, a small molecule that selectively binds PRMT5/MTA complex, significantly inhibits the proliferation of MTAP-deficient tumors and has a weak toxic effect on normal cells. However, it has been reported that MTAP-deleted tumors did not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma, which might lead to a diminished anti-cancer effect of MRTX1719.
View Article and Find Full Text PDFBiol Pharm Bull
December 2024
Department of Radiation Biosciences, Graduate School of Pharmaceutical Sciences, Tokyo University of Science.
Excessive inflammatory responses to viral infections, known as cytokine storms, are caused by overactivation of endolysosomal Toll-like receptors (TLRs) (TLR3, TLR7, TLR8, and TLR9) and can be lethal, but no specific treatment is available. Some quinoline derivatives with antiviral activity were tried during the recent coronavirus disease 2019 (COVID-19) pandemic, but showed serious toxicity, and their efficacy for treating viral cytokine storms was not established. Here, in order to discover a low-toxicity quinoline derivative as a candidate for controlling virally induced inflammation, we synthesized a series of derivatives of amodiaquine (ADQ), a quinoline approved as an antimalarial, and tested their effects on TLRs-mediated production of inflammatory cytokines and cell viability in vitro.
View Article and Find Full Text PDFChem Biol Interact
December 2024
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080-8555, Japan. Electronic address:
This study focused on the synthesis, structural validation, and evaluation of the antiplasmodial efficacy of brachangobinan A (BA) and its enantiomers, (+)-BA and (-)-BA, as potential antimalarial agents. BA, (+)-BA, and (-)-BA were synthesized through chemical processes and validated via advanced spectroscopic techniques. In vitro studies were conducted to assess their efficacy against Plasmodium falciparum strains 3D7 and K1 by determining their half maximal inhibitory concentration (IC) values, cytotoxicity profiles, and selectivity indices.
View Article and Find Full Text PDFLancet Infect Dis
December 2024
MMV Medicines for Malaria Venture, Geneva, Switzerland.
Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.
Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).
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