Antiviral Effect of 5'-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection.

The understanding that zidovudine (ZDV or azidothymidine, AZT) inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and that chalcogen atoms can increase the bioactivity and reduce the toxicity of AZT has directed our search for the discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their toxic effects on these cells, was evaluated. Cell viability analysis revealed that organoselenium (R3a-R3e) showed lower cytotoxicity than organotellurium (R3f, R3n-R3q), with CC50 ≥ 100 µM. The R3b and R3e were particularly noteworthy for inhibiting viral replication in both cell models and showed better selectivity index. In Vero E6, the EC50 values for R3b and R3e were 2.97 ± 0.62 µM and 1.99 ± 0.42 µM, respectively, while in Calu-3, concentrations of 3.82 ± 1.42 µM and 1.92 ± 0.43 µM (24 h treatment) and 1.33 ± 0.35 µM and 2.31 ± 0.54 µM (48 h) were observed, respectively. The molecular docking calculations were carried out to main protease (Mpro), papain-like protease (PLpro), and RdRp following non-competitive, competitive, and allosteric inhibitory approaches. The in silico results suggested that the organoselenium is a potential non-competitive inhibitor of RdRp, interacting in the allosteric cavity located in the palm region. Overall, the cell-based results indicated that the chalcogen-zidovudine derivatives were more potent than AZT in inhibiting SARS-CoV-2 replication and that the compounds R3b and R3e play an important inhibitory role, expanding the knowledge about the promising therapeutic capacity of organoselenium against COVID-19.

Activity of compounds derived from benzofuroxan in Trichomonasvaginalis.

Trichomoniasis is a sexually transmitted infection caused by the protozoan Trichomonas vaginalis. Currently, trichomoniasis is treated with the class of nitroimidazoles, namely, metronidazole; however, resistant isolates and strains have been reported. The compounds derived from benzofuroxan are biologically active heterocycles. This study evaluated the in vitro antiparasitic activity of these compounds in trophozoites of T. vaginalis and determined the mean inhibitory concentration (IC50), minimum inhibitory concentration (MIC), mortality curve, and cytotoxicity. The compounds were named EH1, EH2, EH3, and EA2 and tested in various concentrations: 100 to 15 µM (EH1 and EH2); 100 to 5 µM (EH3); and 100 to 25 µM (EA2), respectively. The greatest efficacy was observed in the highest concentrations in 24 h, with inhibition of approximately 100% of trophozoites. Compounds EH2 and EH3 had the lowest MIC: EH2 (35 µM) and EH3 (45 µM), with IC50 of 11.33 µM and 6.83 µM, respectively. Compound EA2 was effective at the highest concentrations. The activity of the compounds in T. vaginalis started in the first hour of incubation with 90% inhibition; after 12 h, inhibition >95% was observed. Compound EH1 showed the lowest activity, with the highest activity between 12 and 24 h after incubation. These results demonstrate that benzofuroxan derivatives are promising compounds for the in vitro treatment of T. vaginalis.