Synthesis, characterization and antimalarial activity of isoquinoline derivatives
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02642-0
ORIGINAL RESEARCH
Synthesis, characterization and antimalarial activity of isoquinoline derivatives Sewan Theeramunkong
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Artitiya Thiengsusuk2 Opa Vajragupta3 Phunuch Muhamad4 ●
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Received: 5 April 2020 / Accepted: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract This paper presents synthesis of novel decorated isoquinolines that can be used as antimalarial agents. Two series of compounds, isoquinoline phenyl and isoquinoline triazole derivatives, were synthesized via the Suzuki–Miyaura and Sharpless–Fokin reactions respectively. The final compounds were investigated for their antimalarial activity in cell-based experiments. In the series of isoquinoline phenyl derivatives, compound 6 exhibited interesting antiplasmodial activity against chloroquine resistant (K1) and chloroquine sensitive (3D7) strains of P. Falciparum with IC50 1.91 ± 0.21 μM and 2.31 ± 0.33 μM, respectively. In the series of isoquinoline-triazole derivatives, compound 15 was the most active against resistant (K1) and sensitive (3D7) strains of P. falciparum with IC50 4.55 ± 0.10 μM and 36.91 ± 2.83 μM, respectively. The respective resistance indices of compounds 6 and 15 against K1 and 3D7 were 0.83 and 0.12. Compound 15 was promisingly effective against the resistant strain. The results of this study provided useful contributions for further lead discovery and lead modification of modern rational drug design. Keywords Antimalarial activity Plasmodium falciparum Chloroquine resistant Isoquinoline 1,2,3-triazole ●
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Abbreviations P. Plasmodium Pfcrt Plasmodium falciparum chloroquine resistant transporter
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02642-0) contains supplementary material, which is available to authorized users. * Sewan Theeramunkong [email protected] 1
Thammasat University Research Unit in Drug, Health Product Development and Application (DHP-DA), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Bangkok, Pathumthani 12120, Thailand
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Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, 99 Moo 18 Phahonyothin Road, Klongluang, Bangkok, Pathumthani 12120, Thailand
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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Road, Rajathevi, Bangkok 10400, Thailand
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Drug Discovery and Development Center, Office of Advanced Science and Technology, Thammasat University, 99 Moo 18 Phahonyothin Road, Klongluang, Bangkok, Pathumthani 12120, Thailand
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Pfmdr1
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Plasmodium falciparum multidrug resistance 1
Introduction Malaria is a major disease and public health concern. It is mainly prevalent in Africa, South-East Asia and the Eastern Mediterranean. Malaria is caused by Plasmodium parasite. The main transmission vector is the female Ano
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