Six 1,4-benzothiazin-3-ones
(2a–f) and four benzothiazinyl acetate
derivatives (3a–d) were synthesized
and characterized by various
spectroscopic
methods, namely, 1H NMR, 13C NMR, IR, MS, and
elemental analysis. The cytotoxic effects of the compounds were assessed
against MCF-7, a human breast cancer cell line, along with their anti-inflammatory
activity. Molecular docking studies performed against the VEGFR2 kinase
receptor displayed a common binding orientation of the compounds in
the catalytic binding pocket of the receptor. The generalized Born
surface area (GBSA) studies of compound 2c with the highest
docking score also proved its stability in binding to the kinase receptor.
Compounds 2c and 2b showed better results
against VEGFR2 kinase with IC50 values of 0.0528 and 0.0593
μM, respectively, compared to sorafenib. All of the compounds
(2a–f and 3a–d) showed effective growth inhibition having (IC50) values of 2.26, 1.37, 1.29, 2.30, 4.98, 3.7, 5.19, 4.50, 4.39,
and 3.31 μM, respectively, against the MCF-7 cell line compared
to standard 5-fluorouracil (IC50 = 7.79 μM). However,
compound 2c displayed remarkable cytotoxic activity (IC50 = 1.29 μM), suggesting it as a lead compound in the
cytotoxic assay. Additionally, compounds 2c and 2b showed better results against VEGFR2 kinase with IC50 values
of 0.0528 and 0.0593 μM, respectively, compared to sorafenib.
It also inhibited hemolysis by stabilizing the membrane comparable
to that of diclofenac sodium, a standard used in the human red blood
cell membrane stabilization assay and hence can act as a template
for designing novel anticancer and anti-inflammatory agents.
