Structure based virtual and in vitroscreening of active compounds
In our study, structure based virtual screening of 6427 compounds generated 134 hits against SK. Of these, 44 compounds with good binding energy were analyzed by in vitro studies. Of these, 44 compounds with good binding energy were analyzed by in vitro studies (Figure 1A). MABA and MGIT were used for the in vitro study against Mtb using protocol described earlier. 8 Of all 44 compounds seven exhibiting >55% inhibition at 25µg/ml (table 1) and four were active against H37Rv at ≤3.12µg/ml (table 2). The docking studies also showed that all the four hits also have active binding affinity with SK (Figure 1B). The most interacted residues include Glycine, Serine, Isoleucine, Aspartate, Arginine and Alanine, which are present in active region and form hydrogen bond with each hit. The compounds were evaluated for their cytotoxicity in Vero/THP1 cells at varying compound concentrations using MABA. This deciphered that S-014-1049 is non-cytotoxic to the cells with selective index of more than 16. Compounds with selective index >10 are appropriate drug candidates (Table 2).