Toxoplasmosis is a zoonosis of great medical importance and a health problem worldwide; it can cause severe clinical manifestations in immunodeficient patients and fetal malformation if congenitally transmitted. Immunocompromised and immunocompetent individuals can manifest deleterious ophthalmic conditions, including blindness. There is no parasitological cure for toxoplasmosis, as the available drugs, pyrimethamine, and sulfadiazine, both targeting the folate metabolism in the protozoa, are only effective in the acute phase. Although the current medication controls the progress of the acute infection, it can lead to allergies and serious adverse effects (Dannemann, 1992; Haverkos, 1987). Besides, the search for selective and potent drugs for toxoplasmosis treatment continues to be urgent, as diverse immunosuppression therapies lead to the risk of reactivation of the chronic form of the infection. Lysine deacetylase (KDACs) inhibitors such as Apicidin, Valproic acid, and Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) have been described in the literature as potential molecules with activity against several parasites (Darkin-Rattray et al., 1996; Jones-Brando et al., 2003; Strobl et al., 2007) of medical and veterinary importance. Compounds previously studied with inhibitory activity on KDAC enzymes presented activity against protozoa belonging to the phylum Apicomplexa such as Plasmodium falciparum (Chua et al., 2017) and Toxoplasma gondii, and the trypanosomatids Leishmania spp and Trypanosoma cruzi.

(Vergnes et al., 2005; Zuma and De Souza, 2018). T. gondii has homologues for KDAC enzymes annotated in its genome, they are the class I KDAC2 and 3; the class II KDAC1 and 5, the class III deacetylases (Sirtuins) Sir2A and Sir2B, which play a crucial role in the remodeling of the chromatin and the cytoplasmic proteins involved in the process of encystment, proliferation, and maintenance of metabolic pathways; as well as, TgKDAC4, a class IV KDAC which is present in the apicoplast (Fragoso et al., 2023; Hakimi and Deitsch, 2007; Sullivan and Hakimi, 2006). These enzymes were grouped according to sequence similarity with yeast KDACs, the presence of the NAD + or Zn2+ cofactors, and the KDACs domains (Vanagas et al., 2012). Previous work showed the selective inhibitor for mammalian KDAC6, Tubastatin A was effective against tachyzoite forms from different strains of T. gondii and bradyzoite forms, with considerable selectivity (Araujo-Silva et al., 2021). Here we identified three more hydroxamate-type molecules (Fig. 1) with high selectivity towards Toxoplasma gondii and characterized the cellular alterations involved in the arrest of parasite proliferation and formation of new daughter cells.