Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles
A variety of benzimidazole by the heterocyclization of orthophenylenediamine were synthesized in 69–86% yields. The synthesized compounds 3a-f and 6a-f were characterized and further investigated as jack bean urease inhibitors. Density functional theory (DFT) studies were performed utilizing the bas...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-10-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020320302 |
| _version_ | 1818533696120029184 |
|---|---|
| author | Hasil Aman Naghmana Rashid Zaman Ashraf Aamna Bibi Hsin-Tsung Chen Nadaraj Sathishkumar |
| author_facet | Hasil Aman Naghmana Rashid Zaman Ashraf Aamna Bibi Hsin-Tsung Chen Nadaraj Sathishkumar |
| author_sort | Hasil Aman |
| collection | DOAJ |
| description | A variety of benzimidazole by the heterocyclization of orthophenylenediamine were synthesized in 69–86% yields. The synthesized compounds 3a-f and 6a-f were characterized and further investigated as jack bean urease inhibitors. Density functional theory (DFT) studies were performed utilizing the basis set B3LYP/6-31G (d, p) to acquire perception into their structural properties. Frontier molecular orbital (FMO) analysis of all compounds 3a–f and 6a-f was computed at the same level of theory to get a notion about their chemical reactivity and stability. The mapping of the molecular electrostatic potential (MEP) over the entire stabilized molecular geometry indicated the reactive centers. They exhibited urease inhibition activity with IC50 between 22 and 99 μM. Compounds containing withdrawing groups on the benzene ring (3d, 6d) were not showing significant urease inhibition. The value obtained for 3a, 3b, 3f had shown their significant urease inhibition for both theoretical and experimental. Notably, the compound having S-configuration (3a) (22.26 ± 6.2 μM) was good as compared to its R enantiomer 3f (31.42 ± 23.3 μM). Despite this, we elaborated the computational studies of the corresponding compounds, to highlight electronic effect which include HOMO, LUMO, Molecular electrostatic potential (MEP) and molecular docking. |
| first_indexed | 2024-12-11T18:02:08Z |
| format | Article |
| id | doaj.art-8db5f06ac3b849a7b8c2ce14c7cfadbe |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-11T18:02:08Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8db5f06ac3b849a7b8c2ce14c7cfadbe2022-12-22T00:55:51ZengElsevierHeliyon2405-84402020-10-01610e05187Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazolesHasil Aman0Naghmana Rashid1Zaman Ashraf2Aamna Bibi3Hsin-Tsung Chen4Nadaraj Sathishkumar5Department of Chemistry, Faculty of Science, Alama Iqbal Open University, Islamabad 44000, Pakistan; Department of Chemistry, School of Science, Chung Yuan Christian University, Taoyuan 32023, Taiwan; Corresponding author.Department of Chemistry, Faculty of Science, Alama Iqbal Open University, Islamabad 44000, PakistanDepartment of Chemistry, Faculty of Science, Alama Iqbal Open University, Islamabad 44000, PakistanDepartment of Chemistry, School of Science, Chung Yuan Christian University, Taoyuan 32023, TaiwanDepartment of Chemistry, School of Science, Chung Yuan Christian University, Taoyuan 32023, TaiwanDepartment of Chemistry, School of Science, Chung Yuan Christian University, Taoyuan 32023, TaiwanA variety of benzimidazole by the heterocyclization of orthophenylenediamine were synthesized in 69–86% yields. The synthesized compounds 3a-f and 6a-f were characterized and further investigated as jack bean urease inhibitors. Density functional theory (DFT) studies were performed utilizing the basis set B3LYP/6-31G (d, p) to acquire perception into their structural properties. Frontier molecular orbital (FMO) analysis of all compounds 3a–f and 6a-f was computed at the same level of theory to get a notion about their chemical reactivity and stability. The mapping of the molecular electrostatic potential (MEP) over the entire stabilized molecular geometry indicated the reactive centers. They exhibited urease inhibition activity with IC50 between 22 and 99 μM. Compounds containing withdrawing groups on the benzene ring (3d, 6d) were not showing significant urease inhibition. The value obtained for 3a, 3b, 3f had shown their significant urease inhibition for both theoretical and experimental. Notably, the compound having S-configuration (3a) (22.26 ± 6.2 μM) was good as compared to its R enantiomer 3f (31.42 ± 23.3 μM). Despite this, we elaborated the computational studies of the corresponding compounds, to highlight electronic effect which include HOMO, LUMO, Molecular electrostatic potential (MEP) and molecular docking.http://www.sciencedirect.com/science/article/pii/S2405844020320302Organic chemistryPharmaceutical chemistryTheoretical chemistryBenzimidazoleUrease inhibitionDensity functional theory |
| spellingShingle | Hasil Aman Naghmana Rashid Zaman Ashraf Aamna Bibi Hsin-Tsung Chen Nadaraj Sathishkumar Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles Heliyon Organic chemistry Pharmaceutical chemistry Theoretical chemistry Benzimidazole Urease inhibition Density functional theory |
| title | Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles |
| title_full | Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles |
| title_fullStr | Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles |
| title_full_unstemmed | Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles |
| title_short | Synthesis, density functional theory (DFT) studies and urease inhibition activity of chiral benzimidazoles |
| title_sort | synthesis density functional theory dft studies and urease inhibition activity of chiral benzimidazoles |
| topic | Organic chemistry Pharmaceutical chemistry Theoretical chemistry Benzimidazole Urease inhibition Density functional theory |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020320302 |
| work_keys_str_mv | AT hasilaman synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles AT naghmanarashid synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles AT zamanashraf synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles AT aamnabibi synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles AT hsintsungchen synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles AT nadarajsathishkumar synthesisdensityfunctionaltheorydftstudiesandureaseinhibitionactivityofchiralbenzimidazoles |