[PubMed] [CrossRef] [Google Scholar] 12

[PubMed] [CrossRef] [Google Scholar] 12. The high activity, low toxicity, stability, low cost of the starting materials, and straightforward synthesis make these compounds appropriate molecules for the development of affordable antileishmanicidal agents. species (27,C30). Due to their antioxidant activity, the Fe-SOD enzyme present in spp. might be a plausible and good target for these compounds. Encouraged by the encouraging results, we postulated that Se moieties can be central scaffolds for designing new compounds for the treatment of infections caused by leishmania. In this work, we report around the leishmanicidal activities (against and antileishmanial evaluation. In the first step, we assayed the biological activities of Se compounds 1 to 48 (Fig. 1) against both the extra- and intracellular forms of two significant species of (Table 1) and (Table 2). Open in a separate windows FIG 1 Chemical structures of the Se compounds offered in this work. Comp., compound. TABLE 1 activities, toxicities, and SIs of the Se derivatives for extra- and intracellular forms of (M) for:activityactivities, toxicities, and SIs for the Se derivatives on extra- and intracellular forms of (M) for:activitywere tested. IC50 values for toxicity against J774.2 macrophages after 72 h were also Rabbit monoclonal to IgG (H+L)(HRPO) calculated to establish the selectivity indexes (SIs). The results obtained for the N-Bis(2-hydroxypropyl)nitrosamine reference drug, meglumine antimonate, were included in all cases for comparison. Biological data evidenced that half of the screened compounds (compounds 8, 9, 10, 11, 13, 15, 17, 18, 20, 21, 24, 26, 29, 33, 35, 37, 38, 42, 43, 44, 45, 46, 47, and 48) showed high levels of bioactivity against N-Bis(2-hydroxypropyl)nitrosamine potential of the tested compounds with respect to that of the reference drug. The number of times that this SI of each substance exceeded the SI of meglumine antimonate can be demonstrated in parentheses. The differences between meglumine antimonate as well as the tested compounds are revealed clearly. Twelve substances (substances 8, 10, 11, 15, 20, 21, 26, 31, 35, 44, 45, and 48) shown significant selectivity index ideals (SIs 7) for both forms. These derivatives exhibited considerably better SI ideals than the research medication for exceeded that of meglumine antimonate by 237-collapse, another data point, that was by far the very best SI worth. Six from the substances (substances 8, 10, 11, 15, 45, and 48) stood out as the utmost energetic and selective substances, showing IC50s less than 5 M alongside SIs greater than 15, and had been selected for even more studies. Taking into consideration their activity against (Desk 2), the outcomes recurred in both varieties and in both extra- and intracellular forms, since substances 8, 10, 11, 15, 45, and 48 demonstrated greater results considerably, with regards to selectivity and activity, than the remaining tested compounds in every full cases. For instance, the SI of substance 8 exceeded that of the research medication by 237- and 60-collapse for the extra- and intracellular types of (Desk 1) and 53- and 41-collapse for (Desk 2); substances 11 and N-Bis(2-hydroxypropyl)nitrosamine 15 had been similarly effective against both varieties of and against both extra- and intracellular forms. Substance 11 got 41- and 28-collapse increases within the SIs for the extra- and intracellular types of(Desk 2). All of those other examined substances presented similar ideals in both varieties, except substance 20, that was effective against however, not and the ones substance plus substance 20 for promastigotes against, chlamydia rate reduced regarding that for the control significantly; furthermore, the six substances (substances 8, 10, 11, 15, 45, and 48) had been also remarkably far better in reducing infectivity than meglumine antimonate. A way of measuring the average amount of amastigotes per contaminated macrophage (Fig. 2C and ?andD)D) resulted in the same summary: all six substances were far better than meglumine antimonate. Open up in another home window FIG 2 Ramifications of Se derivatives 8, 10, 11, 15, 45, and 48 for the prices of disease by and development prices of per contaminated J774.2 macrophage cell (once the substances had been tested in the IC25). Ideals will be the means from three distinct tests. Gluc., Glucantime (meglumine antimonate). Disease prices (Fig. 3A and ?andB)B) as well as the decrease in amastigote amounts (Fig. 3C and ?andD)D) obtained with also showed that, both in.