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).