1,2Department of Pharmaceutical Chemistry, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.
*Corresponding Author: Mr. Naveen Kumar B S, Department of Pharmaceutical Chemistry, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. Email: naveentvmcp85@gmail.com
Background: Benzothiazole is a privileged heterocyclic scaffold widely recognized in medicinal chemistry for its broad-spectrum pharmacological properties, particularly potent anticancer activity. The present study describes the rational design, synthesis, and comprehensive biological evaluation of twelve novel benzothiazole derivatives (BT-1 to BT-12) incorporating diverse pharmacophoric substituents including halogens, nitro groups, hydroxyl groups, and amine functionalities at the 2- and 6-positions.
Methods: All synthesized compounds were characterized by ¹H NMR, ¹³C NMR, IR, HRMS, and elemental analysis. In vitro anticancer evaluation against MCF-7 (breast), A549 (lung), and HeLa (cervical) cancer cell lines was performed using the MTT assay with doxorubicin as reference standard. Molecular docking was performed against EGFR kinase (PDB ID: 1M17) using AutoDock Vina, and ADMET profiling was conducted via SwissADME and pkCSM.
Results: Among the twelve derivatives, BT-7 and BT-9 exhibited the most potent anticancer activity with IC₅₀ values of 8.24 ± 0.31 µM and 9.15 ± 0.27 µM against MCF-7 cells, respectively. Molecular docking yielded binding energies of −9.8 kcal/mol and −9.4 kcal/mol for BT-7 and BT-9, with critical hydrogen bonds to Met793, Thr790, Lys745, and Asp855. ADMET studies confirmed compliance with Lipinski's rule of five and predicted favorable pharmacokinetics.
Conclusion: These results collectively identify BT-7 and BT-9 as promising lead compounds for further anticancer drug development.
Keywords: Benzothiazole; anticancer; MTT assay; molecular docking; ADMET; EGFR; MCF-7; Schiff base; PLGA nanoparticles; drug design.
How To Cite This Article: Naveen KBS, Elumalai E. Design and Synthesis of Novel Benzothiazole Derivatives: Anticancer Evaluation Supported by Molecular Docking and ADMET Studies. Int J Drug Deliv Technol. 2026;16(12s): 839-863. DOI: 10.25258/ijddt.16.12s.101
Source of support: Nil.
Conflict of interest: None