Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa var. glandulosa.
Indolizidine, antiinfective and antiparasitic compounds from Prosopis glandulosa var. glandulosa.
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DOI：
10.1021/np800653z
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发表时间：
2009-01
影响因子：
5.1
通讯作者：
Muhammad, Ilias
中科院分区：
文献类型：
--
作者：
Samoylenko, Volodymyr;Ashfaq, Mohammad K.;Jacob, Melissa R.;Tekwani, Babu L.;Khan, Shabana I.;Manly, Susan P.;Joshi, Vaishali C.;Walker, Larry A.;Muhammad, Ilias
从腺牧豆（Prosopis glandulosa Torr）中分离得到一个新的抗感染和抗寄生虫的有效化合物2，3-二氢-1H-吲哚嗪氯化物（1）。变种腺。还分离了另外三种新的中氮茚（2-4）和一种已知的中氮茚（5），并制备了1-3的二盐酸盐（化合物6、7和8）。通过1D和2D NMR和质谱确定结构。化合物1显示出对新型隐球菌和烟曲霉的有效体外抗真菌活性（IC 50值分别为0.4和3.0 μg/mL），以及对耐甲氧西林金黄色葡萄球菌和胞内分枝杆菌的抗细菌活性（IC 50值分别为0.35和0.9 μg/mL）。1-4对黄瓜枯萎病菌有显著的体外杀菌活性。neoformans（MFCs = 0.63→1.25 μg/mL）和2、3、5对A.烟曲霉毒素（MFC = 0.63→2.5 μg/mL）的效力类似于黄曲霉素B，但比6-8的效力高>2-4倍。在隐球菌病小鼠模型中，以0.0625 mg/Kg/天/ip给药5天后，丙洛昔定（1）显示出有效的体内活性，可消除约76%的隐球菌。与1.5 mg/Kg/天剂量的阿替霉素B相比，脑组织中的新生儿感染率约为83%。化合物1和4对氯喹敏感（D 6）和氯喹抗性（W2）恶性疟原虫株表现出有效的活性和高选择性指数（SI）值，其IC 50值分别为39和95 ng/mL以及42和120 ng/mL;（氯喹，IC 50 = 17和140 ng/mL）。普罗匹洛辛（1）也显示出体内抗疟活性，治疗3天后，对伯氏疟原虫感染小鼠的ED 50值约为2 mg/Kg/天/ip。
A new potent antiinfective and antiparasitic 2,3-dihydro-1H-indolizinium chloride, (1), was isolated from Prosopis glandulosa Torr. var. glandulosa. Three additional new (2–4) and one known (5), indolizidines were also isolated, and the dihydrochloride salts of 1–3 (compounds 6, 7 and 8) were prepared. Structures were determined by 1D and 2D NMR and mass spectra. Compound 1 showed potent in vitro antifungal activity against Cryptococcus neoformans and Aspergillus fumigatus (IC50 values = 0.4 and 3.0 μg/mL, respectively), and antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare (IC50 values of 0.35 and 0.9 μg/mL, respectively). The remarkable in vitro fungicidal activity of 1–4 against C. neoformans (MFCs = 0.63→1.25 μg/mL) and 2, 3, and 5 against A. fumigatus (MFCs = 0.63→2.5 μg/mL) were similar to amphotericin B, but >2–4-fold more potent than 6–8. Prosopilosidine (1) showed potent in vivo activity at 0.0625 mg/Kg/day/ip for 5 days in a murine model of cryptococcosis by eliminating ~76% of C. neoformans infection from brain tissue compared to ~83% with amphotericin B at 1.5 mg/Kg/day. Compounds 1 and 4 exhibited potent activity and high selectivity index (SI) values against chloroquine sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum with IC50 values of 39 and 95 ng/mL, and 42 and 120 ng/mL, respectively; (chloroquine, IC50 = 17 and 140 ng/mL). Prosopilosine (1) also showed in vivo antimalarial activity with an ED50 value of ~2 mg/Kg/day/ip against Plasmodium berghei-infected mice after 3 days of treatment.
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影响因子：
3.8
作者：
Nakano, H;Nakajima, E;Hasegawa, K
通讯作者：
Hasegawa, K
影响因子：
5.1
作者：
Dou, JH;McChesney, JD;Walker, LA
通讯作者：
Walker, LA
影响因子：
4.2
作者：
Nakano, H;Nakajima, E;Hasegawa, K
通讯作者：
Hasegawa, K
影响因子：
1.8
作者：
DATWYLER, P;OTTLONGONI, R;HESSE, M
通讯作者：
HESSE, M
影响因子：
1.9
作者：
Mikus, Judith;Steverding, Dietmar
通讯作者：
Steverding, Dietmar