TY  - JOUR
A1  - Batool, Farwa
A1  - Saeed, Muhammad
A1  - Saleem, Hafiza Nosheen
A1  - Kirschner, Luisa
A1  - Bodem, Jochen
T1  - Facile synthesis and in vitro activity of N-substituted 1,2-benzisothiazol-3(2H)-ones against dengue virus NS2BNS3 protease
JF  - Pathogens
N2  - Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC\(_{50}\) values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
KW  - dengue virus
KW  - direct-acting antivirals
KW  - 1,2-benzisothiazolinone
KW  - drug discovery
KW  - infectivity assays
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236605
SN  - 2076-0817
VL  - 10
IS  - 4
ER  -