Title:Organocatalyzed Synthesis of 5-aryl-1,2,4-triazolidine-3-thione and 1,2, 4-triazospiro-3-thione, Drug-Likeness and Anti-Microbial Studies
Volume: 12
Issue: 3
Author(s): Radhika R. Mane and Kantharaju Kamanna*
Affiliation:
- Department of Chemistry, Rani Channamma University, P-B, NH-4, Belagavi, 591 153, India
Keywords:
Glutamic acid, biodegradable, thiosemicarbazide, anti-microbial, pharmacological, green chemistry.
Abstract:
Background: Heterocyclic compounds emerged promising choice in drug discovery and
clinical research. Among various heterocycles, 5-aryl-1,2,4-triazolidine-3-thione and 1,2,4-triazospiro-
3-thione derivatives also showed important biological applications. Hence, organic chemists
are striving to develop various catalytic routes for the construction of these derivatives.
Method: The present work describes the eco-friendly synthesis of 5-aryl-1,2,4-triazolidine-3-thione
(3a-o) and 1,2,4-triazospiro-3-thione (5p-u) via one-pot Multi-Component Reactions (MCRs) of
substituted aromatic/heteroaromatic aldehyde, isatine and thiosemicarbazide in the presence of organocatalysts
Glutamic acid (Glu) under microwave irradiation. Additionally, the homogeneity of
the selected compounds was confirmed through various spectroscopic techniques such as FT-IR,
1H- 13C-NMR, and LC-MS. Further, the drug-likeness was evaluated using SwissADME software
and the anti-microbial activity of the selected derivatives were tested.
Results: The reaction exhibits good tolerance towards various substituted aromatic/heteroaromatic
aldehydes, isatine, and thiosemicarbazide, resulting in high yields of product isolation (86–92%).
The computational ADME properties of the prepared derivatives were evaluated for their drug-like
properties, along with an assessment of Lipinski’s Rule of Five. Selected derivatives were also
tested for their antimicrobial properties, showing comparable activities.
Conclusion: Overall, this work describes a greener method synthesis of 5-aryl-1,2,4-triazolidine-
3-thione derivatives (3a-o) and 1,2,4-triazospiro-3-thione derivatives (5p-u). The catalysts used are
biodegradable, environmentally friendly organocatalysts that align with green chemistry principles.
The reaction is accelerated by microwave irradiation in the presence of ethanol. The developed
method is simple, allowing for easy separation of the catalyst using hot ethanol and enabling recycling
up to three times without affecting product isolation. The developed protocol offers advantages
such as accessibility, cost-effectiveness, rapid reactions, mild atom economy, and elimination
of hazardous solvents and catalysts usage. Selected derivatives were screened for antimicrobial
activity, evaluated computationally for drug-likeness in silico, and adhered to Lipinski’s rule
of five.
