Abstract
•Novel cycloheptylbenzothiazole-2-carboxamide were designed.•Nine derivatives were successfully synthesised and characterised.•Good inhibitory activity found in TCP1020 bladder cancer cell lines.•Synthesized compounds have good docking score for ligand-protein complex.
Bladder cancer is one of the deadly cancer with 16,390 deaths in 2015-16 alone and 76,960 new cases. The matter of concern is more severe with very limited options of treatment and lack of new drugs, cisplatin and doxorubicin are the only two drugs mostly used in therapy. This situation along with the epidemiological data calls for the development of newer better and safer agents. Herein, we report nine novel benzothiazole derivatives based on structure-based drug discovery and molecular modelling approaches.
Newly designed compounds were synthesized following a four-step reaction and were characterized for structural confirmation. These novel compounds were evaluated on the MTT assay for their in vitro efficiency using the TCP1020 cell lines. These were further analysed for their mechanism of action based on in silico studies.
Two compounds of the series exhibit promising results which are in agreement with the in-silico studies. It was found that the methyl group at the seventh position to the nitrogen decreases the electron affinity of the series and is thus responsible for the activity in 4e. The methyl substituted compound 4e and fluoro substituted compound 4i shows the highest activities with an IC50 of 10.1 ± 0.2 and 7.8 ± 0.7 respectively.