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SYNTHESIS AND ANTIPLASMODIAL EVALUATION OF A NEW TRIOXAQUINE

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dc.contributor.authorMuregi, Francis W.
dc.contributor.authorWamakima, Hannah N.
dc.contributor.authorKirira, Peter G.
dc.contributor.authorNganga, Margaret M.
dc.contributor.authorGimode, Winnie R.
dc.contributor.authorNaicker, Brandon
dc.contributor.authorTukulula, Matshawendile
dc.date.accessioned2024-07-25T06:29:33Z
dc.date.available2024-07-25T06:29:33Z
dc.date.issued2019-01-11
dc.description.abstractThe ultimate objective of this work was to develop a novel antimalarial hybrid drug based on quinoline and trioxane pharmacophoric scaffold that is effective against drug-resistant malaria, especially in the face of emerging resistance against artemisinin based combination therapy (ACT). The synthetic design involved introduction of a linker to 4,7-dichloroquinoline and subsequent coupling with artesunate to form the dual drug. The structure’s molecular formula C30H38N3ClO7 was confirmed by electron spray ionization mass spectrum that showed a molecular ion peaks at m/z 588.24 and 590.24 amu with a relative abundance of 100% and 38.8% respectively against an exact value of 587.24 amu. Through biological studies, it was established that the drug’s antiplasmodial activity (IC50) against chloroquine (CQ)-sensitive (CQS, D6) and CQ-resistant (CQR, W2) isolates (CQS, 6.89 ng mL-1; CQR, 3.62 ng mL-1) was comparable (p>0.05) to that of artesunate (CQR, 6.67 ng mL-1; CQR, 4.04 ng mL-1), currently the most potent antimalarial in the artemisinin family. The drug had a good safety profile, with low percentage inhibition of human HeLa cell proliferation (29%), and IC50 values >10 000 ng mL-1. The findings validate the concept of ‘‘covalent bitherapy’’ as a feasible strategy in antimalarial drug development.
dc.identifier.citation- Wamakima, Hannah - Kirira, Peter - Nganga, Margaret - Gimode, Winnie - Naicker, Brendon - Tukulula, Matshawandile - Muregi, Francis - 2018/04/09 - 26 - 34 - SYNTHESIS AND ANTIPLASMODIAL EVALUATION OF A NEW TRIOXAQUINE - 5 - EUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH ER
dc.identifier.issn394-3211
dc.identifier.urihttps://erepository.mku.ac.ke/handle/123456789/6129
dc.language.isoen
dc.publisherEUROPEAN JOURNAL OF PHARMACEUTICAL AND MEDICAL RESEARCH
dc.subjectlaria
dc.subjectDrug resistance
dc.subjectHybrid drug
dc.subjectCovalent biotherapy
dc.titleSYNTHESIS AND ANTIPLASMODIAL EVALUATION OF A NEW TRIOXAQUINE
dc.typeArticle
dspace.entity.typePublication
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