کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356471 981121 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure–activity relationship studies of manzamine A: Amidation of positions 6 and 8 of the β-carboline moiety
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Structure–activity relationship studies of manzamine A: Amidation of positions 6 and 8 of the β-carboline moiety
چکیده انگلیسی

Twenty manzamine amides were synthesized and evaluated for in vitro antimalarial and antimicrobial activities. The amides of manzamine A (1) showed significantly reduced cytotoxicity against Vero cells, although were less active than 1. The structure–activity analysis showed that linear, short alkyl groups adjacent to the amide carbonyl at position 8 are favored for antimalarial activity, while bulky and cyclic groups at position 6 provided the most active amides. Most of the amides showed potent activity against Mycobacterium intracellulare. The antimicrobial activity profile for position 8 series was similar to that for antimalarial activity profile, in which linear, slightly short alkyl groups adjacent to the amide carbonyl showed improved activity. Two amides 14 and 21, which showed potent antimalarial activity in vitro against Plasmodium falciparum were further evaluated in vivo in Plasmodium berghei infected mice. Oral administration of 14 and 21 at the dose of 30 mg/kg (once daily for three days) caused parasitemia suppression of 24% and 62%, respectively, with no apparent toxicity.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 22, 15 November 2009, Pages 7775–7782
نویسندگان
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