Rani D. Navle, Nirmala V. Shinde, Arti S. Raut, Arshad S. Shaikh*, Sachin K. Bhosle, Avishkar Pawar

Department of Pharmaceutical Chemistry, SMBT College of Pharmacy, Nashik, India

* Address    for  Correspondence:

Arshad S. Shaikh,

Department of Pharmaceutical Chemistry, SMBT College of Pharmacy (affiliated with Savitribai Phule Pune University), Dhamangaon, Nashik, Maharashtra 422403, India 

E-mail: arshdss141@gmail.com, 

ORCID ID- 0009-0005-9708-5526

Abstract

2-Aminobenzothiazole’s planar structure and tendency to bind to a diverse set of oncogenic targets have made 2-aminobenzothiazole a highly sought heterocyclic in research for anticancer agents. In the past 10 years, intense research in medicinal chemistry has clarified that carefully planned substitution for benzothiazole can yield highly efficient and specific anticancer agents. In this critical assessment, we will specifically evaluate both research and efforts related to 2-aminobenzothiazole-based anticancer agents between 2015 and 2024 for their anticancer targets, SAR relationship, and mechanism of action. In particular, we highlight 2-aminobenzothiazole-based compounds targeting CDKs, Aurora kinase, RAF kinase, and various receptor and non-receptor tyrosine kinases such as EGFR, VEGFR-2, CSF1R, MET, FAK, and DYRK2. Besides inhibition of kinase activity, other non-kinase targets are systematically analysed and introduced in this patent review. These include BCL-2 family members, HDACs, epigenetic modifiers (LSD1, NSD1, FTO), HSP90, mutant p53, and DNA topoisomerases. Substitutions at the C-2, C-5, C-6, and C-7 positions of the benzothiazole ring are examined thoroughly about their anticancer properties and target engagement. Also underscored are the existence of commercially available drugs and patented compounds, as well as translational candidates featuring the 2-aminobenzothiazole pharmacophore. The paper emphasises the dual mechanistic targetability of 2-aminobenzothiazole derivatives as valuable lead compounds targeting both kinases and other targets in an innovative manner aimed at future development of targeted anti-cancer therapies.

Keywords  2-Aminobenzothiazole; Anticancer agents; Tyrosine kinase inhibitors; Structure–activity relationship (SAR); Targeted cancer therapy; VEGFR-2/EGFR inhibition; Kinase signalling; Drug design; Heterocyclic scaffolds

PDF  2-Aminobenzothiazole: A Privileged Scaffold for Tyrosine Kinase–Targeted Anticancer Agents.pdf