gametocytes

Compound 42 (Compound 2), an antimalarial agent, effectively inhibits Plasmodium falciparum during the asexual blood stages (IC 50 <0.5μM) and gametocytes (IC 50 is 0.14 μM).

PfCLK3-IN-1 (Compound 4) serves as a covalent inhibitor of the malaria parasite CLK3 (Pf CLK3) under alkaline conditions, with a pEC50 of 7.1. It inhibits the maturation of gametocytes during the sexual stage of the parasite, thereby hindering transmission. Additionally, PfCLK3-IN-1 effectively suppresses the Dd2-B2 clone of the malaria parasite, exhibiting an IC50 of 239.5 nM.

SAL-0010042 is an inhibitor of Plasmodium phosphodiesterase β (PDEβ), effectively blocking the hydrolysis of cAMP and cGMP in gametocytes with an IC50 of 48.9 nM, thereby activating PKG and inhibiting the growth and development of Plasmodium (IC50s for 3D7 and Dd2 are 142 nM and 218 nM, respectively). It also inhibits hPDE5 and hPDE6 with IC50 values of 632 nM and 73 nM, respectively.

MMV674850 exhibits potency against asexual stage parasites, with IC50 values of 2.7 and 4.5 nM. Furthermore, it demonstrates a preferential affinity for early-stage gametocytes, displaying an IC50 value of 4.5 ± 3.6 nM, compared to late-stage gametocytes with an IC50 value of 28.7 ± 0.2 nM.

KDU691 is a PI4K inhibitor.

FNDR-20123 free base, a pioneering and orally administered anti-malarial agent, acts as a Histone Deacetylase (HDAC) inhibitor, displaying potent efficacy with IC50 values of 31 nM for Plasmodium and 3 nM for human HDAC, respectively. It effectively targets both the asexual (IC50=41 nM) and sexual blood stages (IC50=190 nM for male gametocytes) of Plasmodium falciparum. Additionally, FNDR-20123 free base inhibits multiple HDAC isoforms, namely HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with respective IC50 values of 25, 29, 2, 11, and 282 nM, and displays nanomolar inhibitory concentrations against Class III HDAC isoforms [1].

P-orlandin, a fungal metabolite, effectively impedes Plasmodium falciparum infection in mosquitoes by preventing FREP1 from binding to gametocytes or ookinetes [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].

MMV666810, a 2-aminopyrazine analogue of MMV390048, exhibits potent antiplasmodial activity against asexual parasites with an IC50 value of 5.94 nM. It demonstrates enhanced efficacy against late-stage gametocytes with a 3.3-fold higher selectivity relative to early stages (early-stage gametocyte: IC50 603 ± 88 nM; late-stage gametocyte: IC50 179 ± 8 nM).