کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361270 981460 2012 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis of highly potent novel anti-tubercular isoniazid analogues with preliminary pharmacokinetic evaluation
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis of highly potent novel anti-tubercular isoniazid analogues with preliminary pharmacokinetic evaluation
چکیده انگلیسی

Thirty two novel isoniazid analogues were prepared by one-pot three component condensations of isoniazid (INH), 3-mercaptopropionic acid and various aryl/heteroaryl aldehydes. The synthesized compounds were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37Rv (MTB) and cytotoxicity. Among the compounds, compound N-(2-(4-(benzyloxy) phenyl)-4-oxo-1,3-thiazinan-3-yl) isonicotinamide (17) inhibited MTB with MIC of 0.12 μM and was three times more potent than INH. The main pharmacokinetic parameters after intravenous administration (10 mg/kg body weight) in male Wistar rats viz. t½, Kel, mean plasma clearance and mean volume of distribution were found to be 1.14 ± 0.20 h, 0.62 ± 0.10 h−1, 22.48 ± 0.16 mL/kg/min and 1.99 ± 0.49 L, respectively. The systemic absorption was slow after oral administration (50 mg/kg body weight). The peak plasma concentration was found to be 1.31 ± 0.06 μg/mL attained in 3 h. The bioavailability was found to be 16.7%.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 8, 15 April 2012, Pages 2764–2767
نویسندگان
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