دورية أكاديمية
Evaluating the activity of N-89 as an oral antimalarial drug.
| العنوان: | Evaluating the activity of N-89 as an oral antimalarial drug. |
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| المؤلفون: | Aly NSM; Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.; Department of Parasitology, Benha Faculty of Medicine, Benha University, Benha 13511, Egypt., Matsumori H; Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan., Dinh TQ; Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan., Sato A; Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.; Department of Biochemistry and Molecular Biology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8530, Japan., Miyoshi SI; Department of Sanitary Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan., Chang KS; Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea., Yu HS; Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Yangsan 626-870, Republic of Korea., Kubota T; Department of Natural Products Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan., Kurosaki Y; Department of Pharmaceutical Formulation Design, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan., Cao DT; Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy, Hai Phong, Vietnam., Rashed GA; Department of Parasitology, Benha Faculty of Medicine, Benha University, Benha 13511, Egypt., Kim HS; Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. |
| المصدر: | Parasites, hosts and diseases [Parasites Hosts Dis] 2023 Aug; Vol. 61 (3), pp. 282-291. Date of Electronic Publication: 2023 Aug 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Korean Society for Parasitology and Tropical Medicine Country of Publication: Korea (South) NLM ID: 9918574074806676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2982-6799 (Electronic) Linking ISSN: 29825164 NLM ISO Abbreviation: Parasites Hosts Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Sŏul : The Korean Society for Parasitology and Tropical Medicine, February 2023- |
| مواضيع طبية MeSH: | Antimalarials*/pharmacology , Folic Acid Antagonists* , Oral Medicine*, Animals ; Mice ; Biological Availability ; Parasitemia/drug therapy |
| مستخلص: | Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated. |
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| معلومات مُعتمدة: | JP22wm0125004 Ministry of Education, Culture, Sports, Science, and Technology; Japan Agency for Medical Research and Development |
| فهرسة مساهمة: | Keywords: New antimalarial candidate; in vivo; oral N-89; pharmacokinetics |
| المشرفين على المادة: | 0 (Antimalarials) 0 (Folic Acid Antagonists) |
| تواريخ الأحداث: | Date Created: 20230830 Date Completed: 20230901 Latest Revision: 20230902 |
| رمز التحديث: | 20230902 |
| مُعرف محوري في PubMed: | PMC10471475 |
| DOI: | 10.3347/PHD.23044 |
| PMID: | 37648233 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2982-6799 |
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| DOI: | 10.3347/PHD.23044 |