Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors
N-Substituted-2-propanamide analogues of 1,3,4-oxadiazole have been synthesized using a multi-step synthetic protocol to explore new therapeutic anti-enzymatic agents. Herein, we have merged sulfonyl, piperidine, oxadiazole and amide into a single unit to synthesize a library of unique compounds, 8a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-11-01
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| Series: | Heterocyclic Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/hc-2022-0169 |
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| author | Iqbal Javed Mallhi Ali Imran ur Rehman Aziz Al-Mijalli Samiah H. un-Nisa Mehr Zafar Fatiqa Shahzad Sohail Rasool Shahid Iqbal Munawar Shah Syed Adnan Ali |
| author_facet | Iqbal Javed Mallhi Ali Imran ur Rehman Aziz Al-Mijalli Samiah H. un-Nisa Mehr Zafar Fatiqa Shahzad Sohail Rasool Shahid Iqbal Munawar Shah Syed Adnan Ali |
| author_sort | Iqbal Javed |
| collection | DOAJ |
| description | N-Substituted-2-propanamide analogues of 1,3,4-oxadiazole have been synthesized using a multi-step synthetic protocol to explore new therapeutic anti-enzymatic agents. Herein, we have merged sulfonyl, piperidine, oxadiazole and amide into a single unit to synthesize a library of unique compounds, 8a–n. The molecular structures of all synthesized compounds were verified by 13C-NMR, 1H-NMR, HRMS and IR spectroscopy. Furthermore, the compounds were screened for their inhibition potential against acetylcholinesterase (AChE), urease and lipoxygenase (LOX) enzymes. A considerable inhibition potential was observed for three compounds against LOX with quercetin as a reference standard, two compounds against urease with thiourea as a reference standard and two compounds against AChE with eserine as a reference standard. Through molecular docking investigations, we were able to correlate the overall impact and inhibition criteria by the structure–activity relationship via the interactions between synthesized compounds and active sites of enzymes. Pharmacodynamics, pharmacokinetics and in vivo studies may be investigated further for the most active compounds to substantiate them as potential anti-enzymatic medications. |
| first_indexed | 2024-03-10T18:23:01Z |
| format | Article |
| id | doaj.art-aeaea3079c1e4d7bb0fd8af8ec0e2491 |
| institution | Directory Open Access Journal |
| issn | 2191-0197 |
| language | English |
| last_indexed | 2024-03-10T18:23:01Z |
| publishDate | 2023-11-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Heterocyclic Communications |
| spelling | doaj.art-aeaea3079c1e4d7bb0fd8af8ec0e24912023-11-20T07:16:13ZengDe GruyterHeterocyclic Communications2191-01972023-11-012911496010.1515/hc-2022-0169Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitorsIqbal Javed0Mallhi Ali Imran1ur Rehman Aziz2Al-Mijalli Samiah H.3un-Nisa Mehr4Zafar Fatiqa5Shahzad Sohail6Rasool Shahid7Iqbal Munawar8Shah Syed Adnan Ali9Department of Chemistry, The University of Sahiwal, Sahiwal57000, PakistanDepartment of Applied Chemistry, Government College University, Faisalabad, PakistanDepartment of Chemistry, Government College University, Lahore, Lahore54000, PakistanDepartment of Biology, College of Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDeparatment of Chemistry, University of Lahore, Lahore-54000, PakistanDepartment of Chemistry, The University of Sahiwal, Sahiwal57000, PakistanDepartment of Chemistry, The University of Sahiwal, Sahiwal57000, PakistanDepartment of Chemistry, Government College University, Lahore, Lahore54000, PakistanDepartment of Chemistry, Division of Science and Technology, University of Education, Lahore, PakistanFaculty of Pharmacy, Universiti Teknologi, MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam 42300, Selangor, MalaysiaN-Substituted-2-propanamide analogues of 1,3,4-oxadiazole have been synthesized using a multi-step synthetic protocol to explore new therapeutic anti-enzymatic agents. Herein, we have merged sulfonyl, piperidine, oxadiazole and amide into a single unit to synthesize a library of unique compounds, 8a–n. The molecular structures of all synthesized compounds were verified by 13C-NMR, 1H-NMR, HRMS and IR spectroscopy. Furthermore, the compounds were screened for their inhibition potential against acetylcholinesterase (AChE), urease and lipoxygenase (LOX) enzymes. A considerable inhibition potential was observed for three compounds against LOX with quercetin as a reference standard, two compounds against urease with thiourea as a reference standard and two compounds against AChE with eserine as a reference standard. Through molecular docking investigations, we were able to correlate the overall impact and inhibition criteria by the structure–activity relationship via the interactions between synthesized compounds and active sites of enzymes. Pharmacodynamics, pharmacokinetics and in vivo studies may be investigated further for the most active compounds to substantiate them as potential anti-enzymatic medications.https://doi.org/10.1515/hc-2022-01691,3,4-oxadiazolepiperidinelipoxygenaseureaseacetyl cholinesterase |
| spellingShingle | Iqbal Javed Mallhi Ali Imran ur Rehman Aziz Al-Mijalli Samiah H. un-Nisa Mehr Zafar Fatiqa Shahzad Sohail Rasool Shahid Iqbal Munawar Shah Syed Adnan Ali Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors Heterocyclic Communications 1,3,4-oxadiazole piperidine lipoxygenase urease acetyl cholinesterase |
| title | Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors |
| title_full | Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors |
| title_fullStr | Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors |
| title_full_unstemmed | Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors |
| title_short | Design and synthesis of various 1,3,4-oxadiazoles as AChE and LOX enzyme inhibitors |
| title_sort | design and synthesis of various 1 3 4 oxadiazoles as ache and lox enzyme inhibitors |
| topic | 1,3,4-oxadiazole piperidine lipoxygenase urease acetyl cholinesterase |
| url | https://doi.org/10.1515/hc-2022-0169 |
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