Understanding the Antiplasmodial Action of Resistance-Refractory Xanthoquinodin A1.

Autor: Collins JE; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States., Jiang T; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States., Lee JW; College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea., Wendt K; Department of Chemistry and Biochemistry, Institute for Natural Products Applications & Research Technologies, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019, United States., Nardella F; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States., Jeon J; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, United States., Paes R; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States., Santos NM; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States., Rocamora F; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States., Chang M; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States., Schaefer S; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States., Cichewicz RH; Department of Chemistry and Biochemistry, Institute for Natural Products Applications & Research Technologies, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019, United States., Winzeler EA; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California 92093, United States., Chakrabarti D; Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826, United States.
Jazyk: angličtina
Zdroj: ACS infectious diseases [ACS Infect Dis] 2024 Jun 14; Vol. 10 (6), pp. 2276-2287. Date of Electronic Publication: 2024 May 29.
DOI: 10.1021/acsinfecdis.4c00232
Abstrakt: Our previous work identified a series of 12 xanthoquinodin analogues and 2 emodin-dianthrones with broad-spectrum activities against Trichomonas vaginalis , Mycoplasma genitalium , Cryptosporidium parvum , and Plasmodium falciparum . Analyses conducted in this study revealed that the most active analogue, xanthoquinodin A1, also inhibits Toxoplasma gondii tachyzoites and the liver stage of Plasmodium berghei , with no cross-resistance to the known antimalarial targets PfACS, PfCARL, PfPI4K, or DHODH. In Plasmodium , inhibition occurs prior to multinucleation and induces parasite death following 12 h of compound exposure. This moderately fast activity has impeded resistance line generation, with xanthoquinodin A1 demonstrating an irresistible phenotype in both T. gondii and P. falciparum .
Databáze: MEDLINE