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使用与氨基喹啉相连的类固醇提高杀利什曼原虫和抗结核活性。

Increase of leishmanicidal and tubercular activities using steroids linked to aminoquinoline.

作者信息

Antinarelli Luciana Mr, Carmo Arturene Ml, Pavan Fernando R, Leite Clarice Queico F, Da Silva Adilson D, Coimbra Elaine S, Salunke Deepak B

机构信息

Departamento de Química, I,C,E,, Universidade Federal de Juiz de Fora, Campus Universitário, Juiz de Fora, MG 36036-900, Brazil.

出版信息

Org Med Chem Lett. 2012 May 2;2(1):16. doi: 10.1186/2191-2858-2-16.

DOI:10.1186/2191-2858-2-16
PMID:22551300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3566914/
Abstract

BACKGROUND

Aminoquinoline/steroid conjugates were synthesized based on the fact that steroid transporters have been shown to accept and carry a variety of drugs. So, in continuing our research of antileishmanial and antitubercular drugs, aminoquinoline/steroid conjugates (12, 13, and 14) were regioselectively synthesized via 1, 3-dipolar cycloaddition of alkynes 3, 5, and 7 with azide 12. The aminoquinoline/steroids conjugates were evaluated in vitro against Leishmania major and Mycobacterium tuberculosis.

RESULTS

Regioselective synthesis of the novel aminoquinoline/steroid conjugates was achieved in very high yield. All aminoquinoline/steroid conjugates (12, 13, and 14) exhibited best results against Leishmania and M. tuberculosis than the respective alkyne intermediate structures (3, 5, and 7, respectively). Among them, the compound 12 exhibited the best activity for M. tuberculosis (MIC = 8.8 μM). This result is comparable to drugs commonly used in tuberculosis treatment. Also, for antileishmanial assay, the aminoquinoline/steroid conjugates demonstrated a significant activity against promastigote and amastigote forms of L. major.

CONCLUSIONS

Addition of a steroid group to aminoquinoline molecules enhanced the leishmanicidal and antitubercular activities. These results highlight the importance of steroids as carrier.

摘要

背景

基于甾体转运蛋白已被证明能接受并运载多种药物这一事实，合成了氨基喹啉/甾体缀合物。因此，在继续我们对抗利什曼原虫和抗结核药物的研究中，通过炔烃3、5和7与叠氮化物12的1,3 -偶极环加成反应，区域选择性地合成了氨基喹啉/甾体缀合物（12、13和14）。对氨基喹啉/甾体缀合物进行了体外抗杜氏利什曼原虫和结核分枝杆菌的评估。

结果

以非常高的产率实现了新型氨基喹啉/甾体缀合物的区域选择性合成。所有氨基喹啉/甾体缀合物（12、13和14）对利什曼原虫和结核分枝杆菌的效果均优于各自的炔烃中间体结构（分别为3、5和7）。其中，化合物12对结核分枝杆菌表现出最佳活性（MIC = 8.8 μM）。这一结果与结核病治疗中常用的药物相当。此外，在抗利什曼原虫试验中，氨基喹啉/甾体缀合物对杜氏利什曼原虫的前鞭毛体和无鞭毛体形式均表现出显著活性。

结论

在氨基喹啉分子上添加甾体基团增强了抗利什曼原虫和抗结核活性。这些结果突出了甾体作为载体的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/040019c724a8/2191-2858-2-16-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/e35ea2ee22ec/2191-2858-2-16-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/093c61856e06/2191-2858-2-16-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/26ce92e121ad/2191-2858-2-16-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/040019c724a8/2191-2858-2-16-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/e35ea2ee22ec/2191-2858-2-16-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/093c61856e06/2191-2858-2-16-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/26ce92e121ad/2191-2858-2-16-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a7/3566914/040019c724a8/2191-2858-2-16-4.jpg

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