Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens
A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (<b>2</b>) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized d...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/2/342 |
| _version_ | 1797491622410190848 |
|---|---|
| author | Ihsan A. Shehadi Mohamad T. Abdelrahman Mohamed Abdelraof Huda R. M. Rashdan |
| author_facet | Ihsan A. Shehadi Mohamad T. Abdelrahman Mohamed Abdelraof Huda R. M. Rashdan |
| author_sort | Ihsan A. Shehadi |
| collection | DOAJ |
| description | A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (<b>2</b>) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Proteus vulgaris</i>, <i>Bacillus subtilis</i>, <i>Staphylococcus aureus</i>, and <i>Candida albicans</i>. However, compounds <b>3</b> and <b>5</b> showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds <b>4</b> and <b>6</b>, or only antifungal activity like compound <b>7</b>. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound <b>3</b> showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (−8.4 and −9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound <b>3</b> is a good candidate for the next steps of the drug development process as an antimicrobial drug. |
| first_indexed | 2024-03-10T00:51:56Z |
| format | Article |
| id | doaj.art-7d0f033fadbf428aa6d155dbc69a6105 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T00:51:56Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7d0f033fadbf428aa6d155dbc69a61052023-11-23T14:50:30ZengMDPI AGMolecules1420-30492022-01-0127234210.3390/molecules27020342Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial PathogensIhsan A. Shehadi0Mohamad T. Abdelrahman1Mohamed Abdelraof2Huda R. M. Rashdan3Pure and Applied Chemistry Research Group, Department of Chemistry, College of Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab EmiratesNuclear Research Centre, Radioisotopes Department, Egyptian Atomic Energy Authority, Cairo P.O. Box 12622, EgyptNational Research Centre, Microbial Chemistry Department, Biotechnology Research Institute, 33 El Bohouth St. (Former El Tahrir St.), Giza P.O. Box 12622, EgyptNational Research Centre, Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, Dokki, Cairo P.O. Box 12622, EgyptA new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (<b>2</b>) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Proteus vulgaris</i>, <i>Bacillus subtilis</i>, <i>Staphylococcus aureus</i>, and <i>Candida albicans</i>. However, compounds <b>3</b> and <b>5</b> showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds <b>4</b> and <b>6</b>, or only antifungal activity like compound <b>7</b>. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound <b>3</b> showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (−8.4 and −9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound <b>3</b> is a good candidate for the next steps of the drug development process as an antimicrobial drug.https://www.mdpi.com/1420-3049/27/2/342grindstone chemistry1,3,4-thiadiazolesantimicrobialMICmolecular dockingmolecular dynamics simulations |
| spellingShingle | Ihsan A. Shehadi Mohamad T. Abdelrahman Mohamed Abdelraof Huda R. M. Rashdan Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens Molecules grindstone chemistry 1,3,4-thiadiazoles antimicrobial MIC molecular docking molecular dynamics simulations |
| title | Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens |
| title_full | Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens |
| title_fullStr | Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens |
| title_full_unstemmed | Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens |
| title_short | Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens |
| title_sort | solvent free synthesis in vitro and in silico studies of novel potential 1 3 4 thiadiazole based molecules against microbial pathogens |
| topic | grindstone chemistry 1,3,4-thiadiazoles antimicrobial MIC molecular docking molecular dynamics simulations |
| url | https://www.mdpi.com/1420-3049/27/2/342 |
| work_keys_str_mv | AT ihsanashehadi solventfreesynthesisinvitroandinsilicostudiesofnovelpotential134thiadiazolebasedmoleculesagainstmicrobialpathogens AT mohamadtabdelrahman solventfreesynthesisinvitroandinsilicostudiesofnovelpotential134thiadiazolebasedmoleculesagainstmicrobialpathogens AT mohamedabdelraof solventfreesynthesisinvitroandinsilicostudiesofnovelpotential134thiadiazolebasedmoleculesagainstmicrobialpathogens AT hudarmrashdan solventfreesynthesisinvitroandinsilicostudiesofnovelpotential134thiadiazolebasedmoleculesagainstmicrobialpathogens |