Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors
Abstract Novel N-arylacetamides 2a–f were synthesized based on benzo[d]thiazole scaffold. The compounds 2a–c underwent Knoevenagel condensation through green synthetic method with different aromatic aldehydes and pyrazole-7-carbaldehydes delivered the respective arylidenes with efficient yields. Ary...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13065-025-01386-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832572079465037824 |
|---|---|
| author | Nadia Hanafy Metwally Galal Hamza Elgemeie Aya Ragab Abdelrazek Salwa Magdy Eldaly |
| author_facet | Nadia Hanafy Metwally Galal Hamza Elgemeie Aya Ragab Abdelrazek Salwa Magdy Eldaly |
| author_sort | Nadia Hanafy Metwally |
| collection | DOAJ |
| description | Abstract Novel N-arylacetamides 2a–f were synthesized based on benzo[d]thiazole scaffold. The compounds 2a–c underwent Knoevenagel condensation through green synthetic method with different aromatic aldehydes and pyrazole-7-carbaldehydes delivered the respective arylidenes with efficient yields. Arylidenes 4 reacted with malononitrile affording the corresponding N-arylpyridones 11a–i. Moreover, the reaction of 2a–c with each of salicylaldehyde and 5-arylazo salicylaldehydes afforded the unexpected coumarins rather than quinolin-5-ones. The structure of coumarin 8 was confirmed by density functional theory (DFT) calculations using basis set B3LYP/6-311 G + + (d,p) to obtain the suitable geometrical structure with molecular orbitals` energies revealing its planar structure and its agreement with experimental data. Besides, the antibacterial activity was tested against different bacterial strains revealing potent activity especially Gram-negative bacteria with excellent minimum inhibition concentration (MIC) value ranging from 31.25 to 250 µg/L. Additionally, compounds 2c and 4m showed enzyme inhibition against dihydrofolate reductase in Escherichia coli with greater potency (IC50 for 2c = 3.796 µM, IC50 for 4m = 2.442 µM) than the standard antibiotic trimethoprim (IC50 = 8.706 µM). Investigation of the physicochemical properties of the newly compounds exhibited their better ADME properties that can be developed for the discovery of new antibacterial agents. Graphical Abstract |
| format | Article |
| id | doaj-art-8382c7cc53244011b517f24df576d72d |
| institution | Kabale University |
| issn | 2661-801X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj-art-8382c7cc53244011b517f24df576d72d2025-02-02T12:06:50ZengBMCBMC Chemistry2661-801X2025-01-0119112210.1186/s13065-025-01386-5Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitorsNadia Hanafy Metwally0Galal Hamza Elgemeie1Aya Ragab Abdelrazek2Salwa Magdy Eldaly3Chemistry Department, Faculty of Science, Cairo UniversityChemistry Department, Faculty of Science, Helwan UniversityChemistry Department, Faculty of Science, Cairo UniversityChemistry Department, Faculty of Science, Cairo UniversityAbstract Novel N-arylacetamides 2a–f were synthesized based on benzo[d]thiazole scaffold. The compounds 2a–c underwent Knoevenagel condensation through green synthetic method with different aromatic aldehydes and pyrazole-7-carbaldehydes delivered the respective arylidenes with efficient yields. Arylidenes 4 reacted with malononitrile affording the corresponding N-arylpyridones 11a–i. Moreover, the reaction of 2a–c with each of salicylaldehyde and 5-arylazo salicylaldehydes afforded the unexpected coumarins rather than quinolin-5-ones. The structure of coumarin 8 was confirmed by density functional theory (DFT) calculations using basis set B3LYP/6-311 G + + (d,p) to obtain the suitable geometrical structure with molecular orbitals` energies revealing its planar structure and its agreement with experimental data. Besides, the antibacterial activity was tested against different bacterial strains revealing potent activity especially Gram-negative bacteria with excellent minimum inhibition concentration (MIC) value ranging from 31.25 to 250 µg/L. Additionally, compounds 2c and 4m showed enzyme inhibition against dihydrofolate reductase in Escherichia coli with greater potency (IC50 for 2c = 3.796 µM, IC50 for 4m = 2.442 µM) than the standard antibiotic trimethoprim (IC50 = 8.706 µM). Investigation of the physicochemical properties of the newly compounds exhibited their better ADME properties that can be developed for the discovery of new antibacterial agents. Graphical Abstracthttps://doi.org/10.1186/s13065-025-01386-5SynthesisADME studiesBenzo[d]thiazoleCoumarinsN-arylpyridoneDFT |
| spellingShingle | Nadia Hanafy Metwally Galal Hamza Elgemeie Aya Ragab Abdelrazek Salwa Magdy Eldaly Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors BMC Chemistry Synthesis ADME studies Benzo[d]thiazole Coumarins N-arylpyridone DFT |
| title | Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors |
| title_full | Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors |
| title_fullStr | Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors |
| title_full_unstemmed | Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors |
| title_short | Synthesis, antibacterial evaluation and in silico studies of novel 2-(benzo[d]thiazol-2-yl)-N-arylacetamides and their derivatives as potential DHFR inhibitors |
| title_sort | synthesis antibacterial evaluation and in silico studies of novel 2 benzo d thiazol 2 yl n arylacetamides and their derivatives as potential dhfr inhibitors |
| topic | Synthesis ADME studies Benzo[d]thiazole Coumarins N-arylpyridone DFT |
| url | https://doi.org/10.1186/s13065-025-01386-5 |
| work_keys_str_mv | AT nadiahanafymetwally synthesisantibacterialevaluationandinsilicostudiesofnovel2benzodthiazol2ylnarylacetamidesandtheirderivativesaspotentialdhfrinhibitors AT galalhamzaelgemeie synthesisantibacterialevaluationandinsilicostudiesofnovel2benzodthiazol2ylnarylacetamidesandtheirderivativesaspotentialdhfrinhibitors AT ayaragababdelrazek synthesisantibacterialevaluationandinsilicostudiesofnovel2benzodthiazol2ylnarylacetamidesandtheirderivativesaspotentialdhfrinhibitors AT salwamagdyeldaly synthesisantibacterialevaluationandinsilicostudiesofnovel2benzodthiazol2ylnarylacetamidesandtheirderivativesaspotentialdhfrinhibitors |