Unknown

Dataset Information

0

Ring Distortion of Vincamine Leads to the Identification of Re-Engineered Antiplasmodial Agents.


ABSTRACT: There is a significant need for new agents to combat malaria, which resulted in ∼409,000 deaths globally in 2019. We utilized a ring distortion strategy to create complex and diverse compounds from vincamine with the goal of discovering molecules with re-engineered biological activities. We found compound 8 (V3b) to target chloroquine-resistant Plasmodium falciparum Dd2 parasites (EC50 = 1.81 ± 0.09 μM against Dd2 parasites; EC50 > 40 μM against HepG2 cells) and established structure-activity relationships for 25 related analogues. New analogue 30 (V3ss, Dd2, EC50 = 0.25 ± 0.004 μM; HepG2, EC50 > 25 μM) was found to demonstrate the most potent activity, which prevents exit on the parasite from the schizont stage of intraerythrocytic development and requires >24 h to kill P. falciparum Dd2 cells. These findings demonstrate the potential that vincamine ring distortion has toward the discovery of novel antimalarial agents and other therapies significant to human health.

SUBMITTER: Norwood VM 

PROVIDER: S-EPMC8359148 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7346850 | biostudies-literature
| S-EPMC5378593 | biostudies-literature
| S-EPMC7917639 | biostudies-literature
| S-EPMC6071861 | biostudies-other
| S-EPMC7666986 | biostudies-literature
| S-EPMC6695747 | biostudies-literature
| S-EPMC6071788 | biostudies-literature
| S-EPMC9731315 | biostudies-literature
| S-EPMC4532874 | biostudies-literature
| S-EPMC8704891 | biostudies-literature