Antileishmanial activity of a series of N²,N⁴-disubstituted quinazoline-2,4-diamines.
Antileishmanial activity of a series of N²,N⁴-disubstituted quinazoline-2,4-diamines.
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DOI：
10.1021/jm5000408
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发表时间：
2014-06-26
影响因子：
7.3
通讯作者：
Manetsch R
中科院分区：
文献类型：
--
作者：
Van Horn KS;Zhu X;Pandharkar T;Yang S;Vesely B;Vanaerschot M;Dujardin JC;Rijal S;Kyle DE;Wang MZ;Werbovetz KA;Manetsch R
合成了一系列N2， n4 -二取代喹唑啉-2,4-二胺，并对多诺瓦利什曼原虫和亚马逊河蛭胞内无尾线虫进行了抑菌试验。结构-活性和结构-性质关系研究部分使用Topliss操作方案进行，以确定新的先导化合物。本研究鉴定出的喹唑啉类化合物除具有良好的理化性质外，EC50值在个位数微摩尔或高纳摩尔范围内。喹唑啉23在小鼠内脏利什曼病模型中也显示出疗效，通过腹腔给药15 mg kg-1 day-1连续5天，可减少37%的肝脏寄生虫病。N2， n4 -二取代喹唑啉-2,4-二胺化合物系列具有抗利什曼病的功效、易于合成和良好的理化性质，是今后开发抗利什曼病药物的理想平台。
A series of N2,N4-disubstituted quinazoline-2,4-diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure–activity and structure–property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg–1 day–1 for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N2,N4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
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影响因子：
3.8
作者：
Hailu A;Musa A;Wasunna M;Balasegaram M;Yifru S;Mengistu G;Hurissa Z;Hailu W;Weldegebreal T;Tesfaye S;Makonnen E;Khalil E;Ahmed O;Fadlalla A;El-Hassan A;Raheem M;Mueller M;Koummuki Y;Rashid J;Mbui J;Mucee G;Njoroge S;Manduku V;Musibi A;Mutuma G;Kirui F;Lodenyo H;Mutea D;Kirigi G;Edwards T;Smith P;Muthami L;Royce C;Ellis S;Alobo M;Omollo R;Kesusu J;Owiti R;Kinuthia J;Leishmaniasis East Africa Platform (LEAP) group
通讯作者：
Leishmaniasis East Africa Platform (LEAP) group
影响因子：
3.5
作者：
Delfin, Dawn A.;Morgan, Rachel E.;Werbovetz, Karl A.
通讯作者：
Werbovetz, Karl A.
影响因子：
5.8
作者：
El Fadili, A;Richard, D;Ouellette, M
通讯作者：
Ouellette, M
影响因子：
2.7
作者：
Agarwal, K. C.;Sharma, Vidisha;Gupta, Suman
通讯作者：
Gupta, Suman
影响因子：
2.7
作者：
RAM, VJ;GOEL, A;KAPIL, A
通讯作者：
KAPIL, A