In a screening of Iranian plants for antiprotozoal activity, an n-hexane extract of the roots of Salvia sahendica potently inhibited the growth of Plasmodium falciparum K1 strain. Subsequent HPLC-based activity profiling led to the identification of seven known and one new abietane-type diterpenoid. Structure elucidation was achieved by analysis of spectroscopic data including 1D and 2D NMR. The absolute configuration of sahandol (7) and sahandone (8) were assigned by comparison of experimental ECD spectra with calculated ECD data, using time-dependent density functional theory and methanol as the solvent. In vitro biological activity against P. falciparum and Trypanosoma brucei rhodesiense STIB 900 strain and cytotoxicity in rat myoblast (L6) cells were determined. The IC50 values of the compounds ranged from 0.8 µM to over 8.8 µM against P. falciparum, and from 1.8 µM to over 32.3 µM against T. brucei rhodesiense. The cytotoxic IC50 values ranged from 0.5-15.5 µM. Selectivity indices for P. falciparum were 0.1 to 18.2, and 0.1 to 1.2 for T. brucei rhodesiense.
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http://dx.doi.org/10.1055/s-0032-1328063 | DOI Listing |
Org Lett
January 2025
Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan.
Human African trypanosomiasis (HAT) is one of the most lethal of the neglected tropical diseases. While the discovery of a novel antitrypanosomal drug is highly desired, the creation of a superior lead compound is challenging. Herein we report ukabamide (), which was isolated from a marine sp.
View Article and Find Full Text PDFClin Microbiol Rev
January 2025
School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement.
View Article and Find Full Text PDFBMC Complement Med Ther
December 2024
Center of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.
Background: Neglected tropical diseases (NTDs) afflict nearly 2 billion people worldwide and are caused by various pathogens, such as bacteria, protozoa, and trypanosoma, prevalent in tropical and subtropical regions. Among the 17 NTDs recognized by the World Health Organization (WHO), protozoal infections caused by Plasmodium, Entamoeba, Leishmania, and Trypanosoma are particularly prominent and pose significant public health. Indonesia, endowed with a rich biodiversity owing to its tropical climate, harbors numerous plant species with potent biological activities that hold promise for therapeutic interventions.
View Article and Find Full Text PDFFront Public Health
December 2024
Macha Research Trust, Choma, Zambia.
ACS Infect Dis
December 2024
Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
The proteasome is essential for eukaryotic cell proteostasis, and inhibitors of the 20S proteasome are progressing preclinically and clinically as antiparasitics. We screened, the causative agent of human and animal African trypanosomiasis, with a set of 27 carmaphycin B analogs, irreversible epoxyketone inhibitors that were originally developed to inhibit the20S (Pf20S). The structure-activity relationship was distinct from that of the human c20S antitarget by the acceptance of d-amino acids at the P3 position of the peptidyl backbone to yield compounds with greatly decreased toxicity to human cells.
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