Muregi, Francis W.Wamakima, Hannah N.Kirira, Peter G.Nganga, Margaret M.Gimode, Winnie R.Naicker, BrandonTukulula, Matshawendile2024-07-252024-07-252019-01-11- 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 ER394-3211https://erepository.mku.ac.ke/handle/123456789/6129The 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.enlariaDrug resistanceHybrid drugCovalent biotherapyArticle