Novel amino- and hydroxy-functionalized 1,2,4-trioxanes and their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice via intramuscular and oral route

被引:0
作者
Yadav, Priyanka [1 ]
Naikade, Niraj Krishna [2 ]
Hassam, Mohammad [2 ]
Singh, Ajit Shankar [2 ]
Singh, Chandan [1 ]
Puri, Sunil K. [3 ]
Verma, Ved Prakash [1 ]
机构
[1] Banasthali Univ, Dept Chem, Banasthali Newai 304022, Rajasthan, India
[2] CSIR Cent Drug Res Inst, Med & Proc Chem Div, Sect 10,Sitapur Rd, Lucknow 226031, India
[3] CSIR Cent Drug Res Inst, Parasitol Div, Sect 10,Sitapur Rd, Lucknow 226031, India
关键词
Photooxygenation; 4-trioxane; beta-hydroxyhydroperoxide; Plasmodium yoelii antimalarial activity; Multidrug resistant; ARTEMISININ; PHOTOOXYGENATION; PEROXIDES; CHEMISTRY; ALCOHOLS; SERIES;
D O I
10.1016/j.bmcl.2023.129561
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Following the economic and social state of humanity, Malaria is categorized as one of the life-threatening illness epidemics in under developed countries. For the eradication of the same, 1,2,4-trioxanes 17a1-a2, 17b1-b2, 17c1-c2 15a-c, 18 and 19 have been synthesized continuing the creation of a novel series. Additionally, these novel compounds were tested for their effectiveness against the multidrug-resistant Plasmodium yoelii nigeriensis in mice model using both oral and intramuscular (im) administration routes. The two most potent compounds of the series, 17a1 and 17a2, demonstrated 100 % protection at 48 mg/kg x 4 days via oral route, which is twice as potent as artemisinin. In this model artemisinin provided 100 % protection at a dose of 48 mg/kg x 4 days and 80 % protection at 24 mg/kg x 4 days via im route.
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页数:7
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