-
5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents
- Back
Document Title
5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents
Author
Jansongsaeng S, Srimongkolpithak N, Pengon J, Kamchonwongpaisan S, Khotavivattana T
Name from Authors Collection
Affiliations
Chulalongkorn University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC)
Type
Article
Source Title
MOLECULES
Year
2021
Volume
26
Issue
6
Open Access
gold, Green Published
Publisher
MDPI
DOI
10.3390/molecules26133991
Format
Abstract
The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a-7h) was synthesized and investigated for their antimalarial activity against Plasmodium falciparum. Most analogs showed improved blood antimalarial activity compared to the original primaquine. To further explore a drug hybrid strategy, a conjugate compound between tetraoxane and the representative 5-phenoxy-primaquine analog 7a was synthesized. In our work, the hybrid compound 12 exhibited almost a 30-fold increase in the blood antimalarial activity (IC50 = 0.38 +/- 0.11 mu M) compared to that of primaquine, with relatively low toxicity against mammalian cells (SI = 45.61). Furthermore, we found that these 5-phenoxy primaquine analogs and the hybrid exhibit significant heme polymerization inhibition, an activity similar to that of chloroquine, which could contribute to their improved antimalarial activity. The 5-phenoxy primaquine analogs and the tetraoxane hybrid could serve as promising candidates for the further development of antimalarial agents.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Chulalongkorn University's fund (Ratchadaphiseksomphot Endowment Fund); Thailand Graduate Institute of Science and Technology (TGIST) scholarship [SCA-CO-2562-9780-TH]; National Science and Technology Development Agency scholarship; National Science and Technology Development Agency Grant [P1750501, P1850116]
License
CC-BY
Rights
Authors
Publication Source
WOS