دورية أكاديمية
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Evaluation of the antiplasmodial efficacy of synthetic 2,5-diphenyloxazole analogs of compounds naturally derived from Oxytropis lanata.

التفاصيل البيبلوغرافية
العنوان: Evaluation of the antiplasmodial efficacy of synthetic 2,5-diphenyloxazole analogs of compounds naturally derived from Oxytropis lanata.
المؤلفون: Ariefta NR; National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, 080-8555, Japan., Narita K; Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan., Murata T; Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan., Nishikawa Y; National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, 080-8555, Japan. Electronic address: nisikawa@obihiro.ac.jp.
المصدر: International journal for parasitology. Drugs and drug resistance [Int J Parasitol Drugs Drug Resist] 2024 Aug; Vol. 25, pp. 100540. Date of Electronic Publication: 2024 Apr 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101576715 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-3207 (Electronic) Linking ISSN: 22113207 NLM ISO Abbreviation: Int J Parasitol Drugs Drug Resist Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier, 2011-
مواضيع طبية MeSH: Antimalarials*/pharmacology , Antimalarials*/therapeutic use , Plasmodium falciparum*/drug effects, Animals ; Mice ; Humans ; Oxazoles/pharmacology ; Inhibitory Concentration 50 ; Fibroblasts/drug effects ; Plasmodium yoelii/drug effects ; Malaria, Falciparum/drug therapy ; Malaria/drug therapy ; Malaria/parasitology ; Male
مستخلص: The persistent prevalence and dissemination of drug-resistant malaria parasites continue to challenge the progress of malaria eradication efforts. As a result, there is an urgent need to search for and develop innovative therapies. In this study, we screened synthetic 2,5-diphenyloxazole analogs from Oxytropis lanata. Among 48 compounds, 14 potently inhibited the proliferation of P. falciparum strains 3D7 (chloroquine-sensitive) and K1 (multidrug-resistant) in vitro, exhibited IC 50 values from 3.38 to 12.65 μM and 1.27-6.19 μM, respectively, and were toxic to human foreskin fibroblasts at 39.53-336.35 μM. Notably, Compounds 31 (2-(2',3'-dimethoxyphenyl)-5-(2″-hydroxyphenyl)oxazole) and 32 (2-(2',3'-dimethoxyphenyl)-5-(2″-benzyloxyphenyl)oxazole) exhibited the highest selectivity indices (SIs) against both P. falciparum strains (3D7/K1), with values > 40.20/>126.58 and > 41.27/> 59.06, respectively. In the IC 50 speed and stage-specific assays, Compounds 31 and 32 showed slow action, along with distinct effects on the ring and trophozoite stages. Microscopy observations further revealed that both compounds impact the development and delay the progression of the trophozoite and schizont stages in P. falciparum 3D7, especially at concentrations 100 times their IC 50 values. In a 72-h in vitro exposure experiment at their respective IC 80 in P. falciparum 3D7, significant alterations in parasitemia levels were observed compared to the untreated group. In Compound 31-treated cultures, parasites shrank and were unable to reinvade red blood cells (RBCs) during an extended 144-h incubation period, even after compound removal from the culture. In vivo assessments were conducted on P. yoelii 17XNL-infected mice treated with Compounds 31 and 32 at 20 mg/kg administered once daily for ten days. The treated groups showed statistically significant lower peaks of parasitemia (Compound 31-treated: trial 1 12.7%, trial 2 15.8%; Compound 32-treated: trial 1 12.7%, trial 2 14.0%) compared to the untreated group (trial 1 21.7%, trial 2 28.3%). These results emphasize the potential of further developing 2,5-diphenyloxazoles as promising antimalarial agents.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
فهرسة مساهمة: Keywords: 2,5-Diphenyloxazoles; Antiplasmodial; Plasmodium falciparum; Plasmodium yoelii
المشرفين على المادة: 0 (Antimalarials)
0 (Oxazoles)
تواريخ الأحداث: Date Created: 20240427 Date Completed: 20240808 Latest Revision: 20240808
رمز التحديث: 20240809
مُعرف محوري في PubMed: PMC11067372
DOI: 10.1016/j.ijpddr.2024.100540
PMID: 38676995
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-3207
DOI:10.1016/j.ijpddr.2024.100540