Dataset Information

Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.

ABSTRACT: Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two ?-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.

SUBMITTER: Sakata Y

PROVIDER: S-EPMC6187406 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.

Sakata Yosuke Y Yabunaka Kosuke K Kobayashi Yuko Y Omiya Hirohisa H Umezawa Naoki N Kim Hye-Sook HS Wataya Yusuke Y Tomita Yoshimi Y Hisamatsu Yosuke Y Kato Nobuki N Yagi Hirokazu H Satoh Tadashi T Kato Koichi K Ishikawa Haruto H Higuchi Tsunehiko T

ACS medicinal chemistry letters 20180924 10

Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two π-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a ...[more]

PMID: 30344903

Dataset Information

Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.

Publications

Potent Antimalarial Activity of Two Arenes Linked with Triamine Designed To Have Multiple Interactions with Heme.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Biotransformation of Lignin by an Artificial Heme Enzyme Designed in Myoglobin With a Covalently Linked Heme Group.
| S-EPMC8201792 | biostudies-literature

Synthesis and antimalarial efficacy of two-carbon-linked, artemisinin-derived trioxane dimers in combination with known antimalarial drugs.
| S-EPMC3630999 | biostudies-literature

Cyclopropyl Carboxamides with Potent Antimalarial Activity
| PRJEB75780 | ENA

Identification, structure-activity relationships and molecular modeling of potent triamine and piperazine opioid ligands.
| S-EPMC2746904 | biostudies-literature

De novo designed cyclic-peptide heme complexes.
| S-EPMC263730 | biostudies-literature

MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis.
| S-EPMC5567135 | biostudies-literature

A Hybrid of Amodiaquine and Primaquine Linked by Gold(I) Is a Multistage Antimalarial Agent Targeting Heme Detoxification and Thiol Redox Homeostasis.
| S-EPMC9229949 | biostudies-literature

Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.
| S-EPMC2876411 | biostudies-literature

C-H Electrophilic (phenylsulfonyl)difluoromethylation of (hetero)arenes with a newly designed reagent.
| S-EPMC8603193 | biostudies-literature

Synthesis and potent antimalarial activity of kalihinol B.
| S-EPMC4415034 | biostudies-literature