Synthesis and molecular docking studies of novel tricyclic and angular tetracyclic benzothiadiazines via sp3‐C‐H activation as potential colon cancer inhibitors

This paper describes the synthesis of tricyclic and tetracyclic benzothiadiazines and their derivatives, which are known for their versatility as bioactive agents. The starting materials were N‐cycloamino‐4‐substituted‐2‐nitrobenzenesulfonamides 8–16, which were prepared through the condensation of...

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Bibliographic Details
Published in:Journal of heterocyclic chemistry 2023-10, Vol.60 (10), p.1738-1759
Main Authors: Kolade, Sherif O, Aina, Oluwafemi S, Gordon, Allen T, Hosten, Eric C, Olasupo, Idris A, Ogunlaja, Adeniyi S, Asekun, Olayinka T, Familoni, Oluwole B
Format: Article
Language:English
Subjects:
Amines
Biological activity
Charcoal
Chemical synthesis
Dioxides
Molecular docking
Palladium
Substitutes
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Summary:This paper describes the synthesis of tricyclic and tetracyclic benzothiadiazines and their derivatives, which are known for their versatility as bioactive agents. The starting materials were N‐cycloamino‐4‐substituted‐2‐nitrobenzenesulfonamides 8–16, which were prepared through the condensation of 4‐substituted‐2‐nitrobenzenesulfonyl chlorides 1–3 and cyclic amines 4–7. The intermediates, N‐cycloamino‐4‐substituted‐2‐sulfanilamides 17–25, were obtained through catalytic hydrogenation of N‐cycloamino‐4‐substituted‐2‐nitrobenzenesulfonamides 8–16 using a 10% palladium‐on‐charcoal catalyst. The potentially bioactive tricyclic and angular tetracyclic 1,2,4‐benzothiadizine dioxides 26–34 were then synthesized via metal‐free intramolecular N‐iodosuccinimide (NIS)‐mediated radical oxidative sp3‐C‐H activation aminative cyclization of N‐cycloamino‐4‐substituted‐2‐sulfanilamides 17–25. The yields were good to excellent (68–93%). Docking studies were conducted for N‐cycloamino‐4‐substituted‐2‐nitrobenzenesulfonamides 8–16, N‐cycloamino‐4‐substituted‐2‐sulfanilamides 17–25, and tricyclic and angular tetracyclic 1,2,4‐benzothiadizine dioxides 26–34 for colon cancer using five protein molecules. The results showed that most of the prepared ligands exhibited higher activity than the reference drugs capecitabine, capecitabine, and fluorouracil. Among the compounds synthesized, KS7, a benzothiadiazine, showed the best activity against 6KRO.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.4715