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An Investigation of Novel Series of 2-Thioxo-1,3-dithiol-carboxamides As Potential Antispasmodic Agents: Design, Synthesis Via Coupling Reactions, Density Functional Theory Calculations, and Molecular Docking

Overview
Journal Molecules
Publisher MDPI
Specialty Biology
Date 2024 Aug 29
PMID 39202934
Authors
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Abstract

This study reports the synthesis of 2-thioxo-1,3-dithiol-carboxamides () under mild conditions at room temperature using HBTU as a coupling agent, which significantly improved amide bond formation. The synthesized compounds were characterized using several analytical techniques, including H and C NMR spectroscopy, and HRMS, confirming their intended structures and structural integrity. A DFT computational study at the B3LYP/6-31G(d,p) level was conducted on the four synthesized compounds to compare their electronic properties and molecular structures. The results showed that these compounds demonstrated antispasmodic effects on jejunum contractions. Molecular docking revealed that compounds and displayed the highest docking scores on potassium and voltage-gated calcium channels and adrenergic receptors. In summary, compounds and exhibit antispasmodic effects, potentially blocking alpha-adrenergic receptors and calcium channels, thus providing a scientific basis for their potential use in treating gastrointestinal disorders.

References
1.
Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View

2.
Wang F, Feng C . Metal-Ion-Mediated Supramolecular Chirality of l-Phenylalanine Based Hydrogels. Angew Chem Int Ed Engl. 2018; 57(20):5655-5659. DOI: 10.1002/anie.201800251. View

3.
Liu X, Shi Y, Ma Y, Zhang C, Dong W, Pan L . Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides. Eur J Med Chem. 2009; 44(7):2782-6. DOI: 10.1016/j.ejmech.2009.01.012. View

4.
Laxmikeshav K, Kumari P, Shankaraiah N . Expedition of sulfur-containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update. Med Res Rev. 2021; 42(1):513-575. DOI: 10.1002/med.21852. View

5.
Lahyaoui M, Diane A, El-Idrissi H, Saffaj T, Rodi Y, Ihssane B . QSAR modeling and molecular docking studies of 2-oxo-1, 2-dihydroquinoline-4- carboxylic acid derivatives as p-glycoprotein inhibitors for combating cancer multidrug resistance. Heliyon. 2023; 9(1):e13020. PMC: 9898678. DOI: 10.1016/j.heliyon.2023.e13020. View