Microwave‐assisted synthesis and antimicrobial activity of novel spiro 1,3,4‐thiadiazolines from isatin derivatives

• Published in: Journal of heterocyclic chemistry Vol. 58; no. 3; pp. 766 - 776
• Main Authors: Costa, Daniel Pereira, Castro, Aleff Cruz, Silva, Girlyanderson Araújo, Lima‐Junior, Claudio Gabriel, Andrade Júnior, Francisco Patricio, Oliveira Lima, Edeltrudes, Vaz, Boniek Gontijo, Silva, Lidya Cardoso
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01-03-2021; Wiley Subscription Services, Inc
• Subjects: Acetylation; Antimicrobial agents; Carbonyls; Fungicides; Heating; Irradiation; Spiro compounds; Substrates; Synthesis
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4213

This work describes the synthesis of spiro 1,3,4‐thiadiazolines from isatin‐β‐thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N‐substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug‐likeness and drug‐score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.