Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches
Diabetes mellitus (DM) poses a major global healthcare challenge, highlighting the need for new treatments beyond current options. Currently available drugs have side effects including weight gain, nausea, vomiting, diarrhea, insulin resistance etc. Therefore, given the benefits of indole derivative...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English English |
| Published: |
Springer Science and Business Media Deutschland GmbH
2025
|
| Subjects: | |
| Online Access: | http://umpir.ump.edu.my/id/eprint/43872/1/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives.pdf http://umpir.ump.edu.my/id/eprint/43872/2/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives%20targeting%20human%20aldose%20reductase%20in%20diabetic%20type%202_In-silico%20approaches_ABS.pdf |
| _version_ | 1825816141642072064 |
|---|---|
| author | Roney, Miah Issahaku, Abdul Rashid Mohammed Nazim, Uddin Wilhelm, Anke Mohd Fadhlizil Fasihi, Mohd Aluwi |
| author_facet | Roney, Miah Issahaku, Abdul Rashid Mohammed Nazim, Uddin Wilhelm, Anke Mohd Fadhlizil Fasihi, Mohd Aluwi |
| author_sort | Roney, Miah |
| collection | UMP |
| description | Diabetes mellitus (DM) poses a major global healthcare challenge, highlighting the need for new treatments beyond current options. Currently available drugs have side effects including weight gain, nausea, vomiting, diarrhea, insulin resistance etc. Therefore, given the benefits of indole derivatives in diabetes and the lack of computational studies on bis-indole-based triazine derivatives with aldose reductase (AR), this study employs in-silico analysis to explore their potential as type-2 diabetes treatments. Based on the Differential Expression analysis, the human aldose reductase (HAR) encoding gene AKR1B1 showed overexpression in GSE30122 diabetes patients (Log2FC = 0.62, P < 0.01). Moreover, the compounds 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(3-hydroxy-5-methylphenyl)ethan-1-one (4) and 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(4-nitrophenyl)ethan-1-one (8) were identified as leading candidates, showing binding energies of − 62.12, − 81.73 kcal/mol and − 57.19, − 85.97 kcal/mol, respectively. Docking, MM/GBSA screening, molecular dynamics (MD) simulations, PCA, and post-MM/GBSA analysis confirmed their stability and favorable binding compared to the apo protein and control. Further in-vitro, in-vivo, and clinical studies are required to validate their therapeutic potential. |
| first_indexed | 2025-03-06T04:06:00Z |
| format | Article |
| id | UMPir43872 |
| institution | Universiti Malaysia Pahang |
| language | English English |
| last_indexed | 2025-03-06T04:06:00Z |
| publishDate | 2025 |
| publisher | Springer Science and Business Media Deutschland GmbH |
| record_format | dspace |
| spelling | UMPir438722025-02-20T05:04:45Z http://umpir.ump.edu.my/id/eprint/43872/ Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches Roney, Miah Issahaku, Abdul Rashid Mohammed Nazim, Uddin Wilhelm, Anke Mohd Fadhlizil Fasihi, Mohd Aluwi HD Industries. Land use. Labor Q Science (General) T Technology (General) Diabetes mellitus (DM) poses a major global healthcare challenge, highlighting the need for new treatments beyond current options. Currently available drugs have side effects including weight gain, nausea, vomiting, diarrhea, insulin resistance etc. Therefore, given the benefits of indole derivatives in diabetes and the lack of computational studies on bis-indole-based triazine derivatives with aldose reductase (AR), this study employs in-silico analysis to explore their potential as type-2 diabetes treatments. Based on the Differential Expression analysis, the human aldose reductase (HAR) encoding gene AKR1B1 showed overexpression in GSE30122 diabetes patients (Log2FC = 0.62, P < 0.01). Moreover, the compounds 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(3-hydroxy-5-methylphenyl)ethan-1-one (4) and 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(4-nitrophenyl)ethan-1-one (8) were identified as leading candidates, showing binding energies of − 62.12, − 81.73 kcal/mol and − 57.19, − 85.97 kcal/mol, respectively. Docking, MM/GBSA screening, molecular dynamics (MD) simulations, PCA, and post-MM/GBSA analysis confirmed their stability and favorable binding compared to the apo protein and control. Further in-vitro, in-vivo, and clinical studies are required to validate their therapeutic potential. Springer Science and Business Media Deutschland GmbH 2025 Article PeerReviewed pdf en http://umpir.ump.edu.my/id/eprint/43872/1/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives.pdf pdf en http://umpir.ump.edu.my/id/eprint/43872/2/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives%20targeting%20human%20aldose%20reductase%20in%20diabetic%20type%202_In-silico%20approaches_ABS.pdf Roney, Miah and Issahaku, Abdul Rashid and Mohammed Nazim, Uddin and Wilhelm, Anke and Mohd Fadhlizil Fasihi, Mohd Aluwi (2025) Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches. 3 Biotech, 15 (5). pp. 1-16. ISSN 2190-572X. (Published) https://doi.org/10.1007/s13205-024-04178-1 https://doi.org/10.1007/s13205-024-04178-1 |
| spellingShingle | HD Industries. Land use. Labor Q Science (General) T Technology (General) Roney, Miah Issahaku, Abdul Rashid Mohammed Nazim, Uddin Wilhelm, Anke Mohd Fadhlizil Fasihi, Mohd Aluwi Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title | Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title_full | Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title_fullStr | Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title_full_unstemmed | Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title_short | Exploration of leads from bis-indole based triazine derivatives targeting human aldose reductase in diabetic type 2: In-silico approaches |
| title_sort | exploration of leads from bis indole based triazine derivatives targeting human aldose reductase in diabetic type 2 in silico approaches |
| topic | HD Industries. Land use. Labor Q Science (General) T Technology (General) |
| url | http://umpir.ump.edu.my/id/eprint/43872/1/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives.pdf http://umpir.ump.edu.my/id/eprint/43872/2/Exploration%20of%20leads%20from%20bis-indole%20based%20triazine%20derivatives%20targeting%20human%20aldose%20reductase%20in%20diabetic%20type%202_In-silico%20approaches_ABS.pdf |
| work_keys_str_mv | AT roneymiah explorationofleadsfrombisindolebasedtriazinederivativestargetinghumanaldosereductaseindiabetictype2insilicoapproaches AT issahakuabdulrashid explorationofleadsfrombisindolebasedtriazinederivativestargetinghumanaldosereductaseindiabetictype2insilicoapproaches AT mohammednazimuddin explorationofleadsfrombisindolebasedtriazinederivativestargetinghumanaldosereductaseindiabetictype2insilicoapproaches AT wilhelmanke explorationofleadsfrombisindolebasedtriazinederivativestargetinghumanaldosereductaseindiabetictype2insilicoapproaches AT mohdfadhlizilfasihimohdaluwi explorationofleadsfrombisindolebasedtriazinederivativestargetinghumanaldosereductaseindiabetictype2insilicoapproaches |