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
Riham Sghyar,
Mouad Lahyaoui,
Noura Aflak,
Oussama Moussaoui,
Alae Chda,
Rachid Bencheikh,
El Mestafa El Hadrami,
Nada Kheira Sebbar,
Ashwag S. Alanazi,
Mohamed Hefnawy
Affiliations
Riham Sghyar
Laboratory of Applied Organic Chemistry, Faculty of Science and Techniques, Sidi Mohamed Ben Abdellah University, Routed ‘Imouzzer, B.P. 2202, Fez 30050, Morocco
Mouad Lahyaoui
Laboratory of Applied Organic Chemistry, Faculty of Science and Techniques, Sidi Mohamed Ben Abdellah University, Routed ‘Imouzzer, B.P. 2202, Fez 30050, Morocco
Noura Aflak
Department of Chemistry, Faculty of Science, University Ibn Zohr, Agadir 80000, Morocco
Oussama Moussaoui
Laboratory of Applied Organic Chemistry, Faculty of Science and Techniques, Sidi Mohamed Ben Abdellah University, Routed ‘Imouzzer, B.P. 2202, Fez 30050, Morocco
Alae Chda
Institut Supérieur Des Professions Infirmières Et Techniques de Santé, Rabat 60000, Morocco
Rachid Bencheikh
Microbial Biotechnology and Bioactive Molecules Laboratory, FST, USMBA, B.P. 2202, Fez 30050, Morocco
El Mestafa El Hadrami
Laboratory of Applied Organic Chemistry, Faculty of Science and Techniques, Sidi Mohamed Ben Abdellah University, Routed ‘Imouzzer, B.P. 2202, Fez 30050, Morocco
Nada Kheira Sebbar
Applied Chemistry and Environment Laboratory, Applied Bioorganic Chemistry Team, Faculty of Science, Ibn Zohr University, Agadir 80000, Morocco
Ashwag S. Alanazi
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Mohamed Hefnawy
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
This study reports the synthesis of 2-thioxo-1,3-dithiol-carboxamides (TDTCAs) 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 1H and 13C 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 c and d displayed the highest docking scores on potassium and voltage-gated calcium channels and adrenergic receptors. In summary, compounds c and d exhibit antispasmodic effects, potentially blocking alpha-adrenergic receptors and calcium channels, thus providing a scientific basis for their potential use in treating gastrointestinal disorders.
