antimalarial agent-1

Antimalarial agent 1 is an effective antimalarial agent.

Mefloquine (Ro 215998), a quinoline antimalarial agent, is an anti-SARS-CoV-2 entry inhibitor. Mefloquine is also a K+ channel (KvQT1 minK) antagonist with an IC50 of ~1 μM. Mefloquine can be used for malaria, systemic lupus erythematosus, and cancer research.

MMV665916 is a quinazolinedione derivative that is an antimalarial agent. MMV665916 shows remarkable antiplasmodial activity against P. falciparum FcB1 strain with EC 50 value of 0.4 μM and presents the high selectivity index (SI>250) [1].

Emoquine-1 is a potent orally active antimalarial agent effective against various drug-resistant Plasmodium strains, including artemisinin-resistant dormant parasites. It demonstrates efficacy against proliferative malignant Plasmodium with an IC50 value ranging from 20 to 55 nM. Emoquine-1 holds potential for treating Plasmodium strains resistant to artemisinin combination therapy (ACT), with the capability to eradicate persistent parasites.

Insecticidal agent 19 (Compound 7b) exhibits antimalarial activity by inhibiting dihydrofolate reductase-thymidylate synthase (DHFR-TS) and pteridine reductase 1 (PTR1) through the folate metabolic pathway. This compound also inhibits the promastigote and amastigote forms of Leishmania major, with IC50 values of 1.43 μM and 3.78 μM, respectively.

Amodiaquine dihydrochloride (Amodiaquin dihydrochloride), a member of the 4-aminoquinoline class, is an antimalarial agent that also acts as a potent oral histamine N-methyltransferase inhibitor with a K i value of 18.6 nM. Additionally, it functions as a Nurr1 agonist, targeting the Nurr1-LBD (ligand binding domain) with an EC 50 of approximately 20 μM, demonstrating anti-inflammatory effects [1] [2] [3] [4] [5].

HLI373 dihydrochloride is a potent Hdm2 inhibitor, efficiently restraining the ubiquitin ligase activity of Hdm2 and effectively prompting apoptosis in DNA-damaging agent-sensitive tumor cells[1]. Additionally, HLI373 dihydrochloride exhibits antimalarial activity[2].

JMI-105 has the potential as an antimalarial agent. JMI-105 is a potent inhibitor of Plasmodium falciparum falcipain-2 protease (PfFP-2) that inhibits the P. falciparum strains CQ S (3D7) and CQ R (RKL-9) growth with IC 50 values of 8.8 μM and 14.3 μM. In a murine model with P. berghei ANKA infection, JMI-105 significantly decreases parasitemia and prolonged host survival [1].

Antimalarial agent 11 (compound 1), a spirocyclic chromane, is a potent antimalarial agent effective against D6 (EC50: 1.48 μM) and ARC08-022 (EC50: 1.81 μM).

Piperaquine tetraphosphate, a potent antimalarial agent, demonstrates inhibitory effects against both chloroquine-sensitive and chloroquine-resistant malaria isolates. When combined with dihydroartemisinin, it holds potential for researching chloroquine-resistant malaria [1] [2].

Hydroxychloroquine Impurity F, an impurity in Hydroxychloroquine, is identified in the synthetic antimalarial agent known for its capability to inhibit Toll-like receptor 7 9 (TLR7 9) signaling. Additionally, Hydroxychloroquine demonstrates effective inhibition of SARS-CoV-2 infection in vitro [1] [2] [3].

Antimalarial agent 17, functioning both as an antimalarial agent and a herbicide, inhibits photosystem II and demonstrates post-emergence herbicidal efficacy comparable to commercial herbicides [1].

Antimalarial agent 23, a benzimidazole-based compound, exhibits potent antimalarial activity, demonstrated by its low IC50 values of 0.08 μM for PfNF54 and 0.10 μM for PfK1, respectively. This compound effectively inhibits β-hematin formation, yet it does not directly interfere with the conversion of heme to hemozoin [1].

Antimalarial agent 19 (compound 6e) exhibits antimalarial activity against the blood stages of P. falciparum K1 and P. berghei, with EC50 values of 0.3 µM and 15.3 µM, respectively. It demonstrates good aqueous solubility, intestinal permeability, and microsomal stability relative to gamhepathiopine [1].

Antimalarial agent 27 (compound 11a) potently inhibits P. falciparum with an IC50 of 0.37 μM, targeting the parasite's 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) enzyme with an IC50 of 0.11 μM, indicating its mechanism of action [1].

Compound 24 (Compound 7), an in vitro antimalarial agent, demonstrates inhibitory activity against the Plasmodium falciparum W2 strain with an IC50 of 0.81 μM and exhibits a cytotoxicity threshold (CC50) exceeding 200 μM in HepG2 cells [1].

Antimalarial agent 26, a derivative of 1,4-naphthoquinones, demonstrates antimalarial properties through oral administration. It exhibits cytotoxic effects on P. falciparum while maintaining selectivity against mammalian cell lines and effectively inhibits P. berghei-induced parasitemia in vivo [1].

Compound 31 (compound 7k) is an orally active inhibitor of Plasmodium falciparum aspartic protease, plasmepsin X (PMX), with antimalarial properties [1].

Antimalarial agent 28 (Compound 2i) is an antiplasmodial agent that inhibits P. berghei with IC50 values of 0.561 μM for the liver stage, 0.14 μM for early gametocytes, and 4.34 μM for the ring stages of P. falciparum [1].

Compound 29 (also known as Compound 16) is an antimalarial agent that demonstrates inhibition of the P. berghei liver stage parasite load, exhibiting an effective concentration (EC50) of 5.2 μM [1].

FIKK9.1-IN-1 (Compound 1), an antimalarial agent (IC50: 2.68 μg mL), serves as a FIKK9.1 inhibitor by interacting with the ATP-binding residues within FIKK9.1, thereby disrupting the parasite life cycle and resulting in parasite death [1].

Antimalarial agent 33 (compound 5g) exhibits antiplasmodial activity targeting both erythrocytic and hepatic stages of Plasmodium, with an effective concentration (EC50) of 1.1 μM against the K1 strain of P. falciparum. It demonstrates improved microsomal stability with a half-life (T1 2) of 29 minutes and displays no significant cytotoxicity against primary hepatocytes [1].

6-Nitroquinazoline, an antimalarial agent, is also a substrate for human liver aldehyde oxidase [1].

Antimalarial agent 25, a derivative of 1,4-naphthoquinones, demonstrates oral activity and is effective against malaria. It exhibits cytotoxic properties specifically targeting P. falciparum and effectively inhibits parasitemia induced by P. burghei in vivo [1].