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-Reference-Cited by-同舟云学术

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

Published:2024-08-14 Issue:16 Volume:29 Page:3855
ISSN:1420-3049
Container-title:Molecules
language:en
Short-container-title:Molecules

Author:

Sghyar Riham¹,Lahyaoui Mouad¹^ORCID,Aflak Noura²³^ORCID,Moussaoui Oussama¹⁴,Chda Alae⁵⁶,Bencheikh Rachid⁶,El Hadrami El Mestafa¹^ORCID,Sebbar Nada Kheira⁷⁸,Alanazi Ashwag S.⁹^ORCID,Hefnawy Mohamed¹⁰

Affiliation:

1. Laboratory of Applied Organic Chemistry, Faculty of Science and Techniques, Sidi Mohamed Ben Abdellah University, Routed ‘Imouzzer, B.P. 2202, Fez 30050, Morocco

2. Department of Chemistry, Faculty of Science, University Ibn Zohr, Agadir 80000, Morocco

3. Laboratory of Analytical and Molecular Chemistry/LAMC, Polydisciplinary Faculty, Cadi Ayyad University, Safi 46030, Morocco

4. Laboratory of Organic Synthesis, Extraction and Valorization, Department of Chemistry, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, B.P. 5366, Casablanca 20670, Morocco

5. Institut Supérieur Des Professions Infirmières Et Techniques de Santé, Rabat 60000, Morocco

6. Microbial Biotechnology and Bioactive Molecules Laboratory, FST, USMBA, B.P. 2202, Fez 30050, Morocco

7. Applied Chemistry and Environment Laboratory, Applied Bioorganic Chemistry Team, Faculty of Science, Ibn Zohr University, Agadir 80000, Morocco

8. Laboratory of Heterocyclic Organic Chemistry, Drug Science Research Center, Pharmacochemistry Competence Center, Faculty of Sciences, Mohammed V University in Rabat, Av. Ibn Battouta, B.P. 1014, Rabat 10000, Morocco

9. Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia

10. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Abstract

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.

Funder

Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

King Saud University, Riyadh 11451, Saudi Arabia

Publisher

MDPI AG

Link

https://www.mdpi.com/1420-3049/29/16/3855/pdf

Reference34 articles.

1. Determination of sulfur heterocycles in coal liquids and shale oils;Willey;Anal. Chem.,1981

2. Expedition of sulfur-containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update;Laxmikeshav;Med. Res. Rev.,2022

3. Gharge, S., and Alegaon, S.G. (2024). Recent Studies of Nitrogen and Sulfur Containing Heterocyclic Analogues as Novel Antidiabetic Agents: A review. Chem. Biodivers., 21.

4. Heterocyclic Compounds: Importance in Anticancer Drug Discovery;Kumar;Anti-Cancer Agents Med. Chem.,2022

5. Micucci, M., Viale, M., Chiarini, A., Spinelli, D., Frosini, M., Tavani, C., and Budriesi, R. (2020). Aryl-4-nitrobenzothiochromans S, S-dioxide: From calcium-channel modulators properties to multidrug-resistance reverting activity. Molecules, 25.