Background: Despite the availability of a variety of chemotherapeutic agents, cancer is still one of
the leading causes of death worldwide because of the problems with existing chemotherapeutic agents like objectionable
side effects, lack of selectivity, and resistance. Hence, there is an urgent need for the development of
novel anticancer agents with high usefulness, fewer side effects, devoid of resistance and superior selectivity.
Objective: The objective of this study is to synthesize a series of novel 1,5-benzothiazepine derivatives and
evaluate their anticancer activity employing biological and computational methods.
Methods: Twenty new benzothiazepines (BT1-BT20) were prepared by condensing different 1-(4-
isobutylphenyl)ethanone chalcones with 2-amiothiophenol and evaluated for their anticancer activity by MTT
assay against three cell lines including HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate
cancer). These compounds were also tested for their inhibitory action against EGFR (Epidermal Growth Factor
Receptor) tyrosine kinase enzyme by taking into account of their excellent action against colon and breast cancer
cell lines. Further, the structural features responsible for the activity were identified by Pharmacophorebased
modelling using Schrodinger’s PHASETM software.
Results: Among the 20 benzothiazepine derivatives, three compounds viz., BT18, BT19 and BT20 exhibited promising
activity against the cell lines tested and the activity of BT20 was more than the standard methotrexate. Again the
above three compounds showed excellent inhibitory activity with the percentage inhibition of 64.5, 57.3 and
55.8 respectively against EGFR (Epidermal Growth Factor Receptor) tyrosine kinase. PHASE identified a five-point
AHHRR model for the proposed activity and the computational studies provided insights into the structural
requirements for the anticancer activity and the results were consistent with the observed in vitro activity data.
Conclusion: These novel benzothiazepines will be useful as lead molecules for the further development of new
cancer therapies against colon and breast cancers.