Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach
The transcription factor family includes the cluster protein signal transducer and activator of transcription 3 (STAT3). Colorectal cancer (CRC) is predisposed to develop and spread when STAT 3 is abnormally activated because it speeds up cell division, prevents differentiation, and suppresses apopt...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715623002096 |
| _version_ | 1797799033650020352 |
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| author | Syeda Mobeen Anjum Katari Sudheer Kumar Amineni Umamaheswari Dinesh Lakhanpal Sandeep Swargam Khateef Riazunnisa Thummala Chandrasekhar |
| author_facet | Syeda Mobeen Anjum Katari Sudheer Kumar Amineni Umamaheswari Dinesh Lakhanpal Sandeep Swargam Khateef Riazunnisa Thummala Chandrasekhar |
| author_sort | Syeda Mobeen Anjum |
| collection | DOAJ |
| description | The transcription factor family includes the cluster protein signal transducer and activator of transcription 3 (STAT3). Colorectal cancer (CRC) is predisposed to develop and spread when STAT 3 is abnormally activated because it speeds up cell division, prevents differentiation, and suppresses apoptosis. Only a small number of phytochemicals such as curcumin have been solidly demonstrated in clinical trials to lower the risk of CRC based on dose as well as confounding variables. Enthused by literature citations, we aimed in the present work to design novel antagonists against STAT3 using phytocompounds of two medicinal plants (Catharanthus roseus and Moringa oleifera) by integration of in-vivo and in-silico strategy. In-silico analysis was intended with receptor STAT3 (PDB ID: 6QHD), ligands (97 tentatively identified GC-MS compounds), and standard drugs (regorafenib and irinotecan) by docking and simulation analysis via tools such as Maestro v.11.9, LigPrep, Epik v.4.7, QikProp v.5.1, Glide v.8.2 of Schrodinger LLC-2019.1, and Desmond v.3.8. Docking studies exemplifies that STAT3 depicted better binding affinity with pyrrole (3,4-C) pyrrole-1-carboxylic acid, octadecanoic acid, and 2,3-dihydroxypropyl ester, (−7.266 kcal/mol, and −7.124 kcal/mol) as compared with standard drugs (regorafenib, and irinotecan). Further, the molecular dynamics analysis of these two lead complexes for 100 ns validates the stability, superiority of the vital interactions and also retained all over the trajectories besides fulfilling the ADMET criteria. Thus, the proposed leads act as valuable starting points and ideal candidates to be developed as drug candidates for CRC patients if synthesized and tested in-vitro, in-vivo, and in animal models after further detailed investigations. |
| first_indexed | 2024-03-13T04:12:49Z |
| format | Article |
| id | doaj.art-b1d2953e3c084fd98e6e198651a13391 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-13T04:12:49Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-b1d2953e3c084fd98e6e198651a133912023-06-21T06:52:45ZengElsevierResults in Chemistry2211-71562023-01-015100970Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approachSyeda Mobeen Anjum0Katari Sudheer Kumar1Amineni Umamaheswari2Dinesh Lakhanpal3Sandeep Swargam4Khateef Riazunnisa5Thummala Chandrasekhar6Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh 516005, IndiaDeparment of Bioinformatics, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh 517507, IndiaDeparment of Bioinformatics, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh 517507, IndiaCentre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Shahpur and Dharamshala, Himachal Pradesh 176206, IndiaCentre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Shahpur and Dharamshala, Himachal Pradesh 176206, India; Corresponding authors.Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh 516005, India; Corresponding authors.Department of Environmental Science, Yogi Vemana University, Kadapa, Andhra Pradesh 516005, IndiaThe transcription factor family includes the cluster protein signal transducer and activator of transcription 3 (STAT3). Colorectal cancer (CRC) is predisposed to develop and spread when STAT 3 is abnormally activated because it speeds up cell division, prevents differentiation, and suppresses apoptosis. Only a small number of phytochemicals such as curcumin have been solidly demonstrated in clinical trials to lower the risk of CRC based on dose as well as confounding variables. Enthused by literature citations, we aimed in the present work to design novel antagonists against STAT3 using phytocompounds of two medicinal plants (Catharanthus roseus and Moringa oleifera) by integration of in-vivo and in-silico strategy. In-silico analysis was intended with receptor STAT3 (PDB ID: 6QHD), ligands (97 tentatively identified GC-MS compounds), and standard drugs (regorafenib and irinotecan) by docking and simulation analysis via tools such as Maestro v.11.9, LigPrep, Epik v.4.7, QikProp v.5.1, Glide v.8.2 of Schrodinger LLC-2019.1, and Desmond v.3.8. Docking studies exemplifies that STAT3 depicted better binding affinity with pyrrole (3,4-C) pyrrole-1-carboxylic acid, octadecanoic acid, and 2,3-dihydroxypropyl ester, (−7.266 kcal/mol, and −7.124 kcal/mol) as compared with standard drugs (regorafenib, and irinotecan). Further, the molecular dynamics analysis of these two lead complexes for 100 ns validates the stability, superiority of the vital interactions and also retained all over the trajectories besides fulfilling the ADMET criteria. Thus, the proposed leads act as valuable starting points and ideal candidates to be developed as drug candidates for CRC patients if synthesized and tested in-vitro, in-vivo, and in animal models after further detailed investigations.http://www.sciencedirect.com/science/article/pii/S2211715623002096STAT3CRCGlideDockingMD simulations |
| spellingShingle | Syeda Mobeen Anjum Katari Sudheer Kumar Amineni Umamaheswari Dinesh Lakhanpal Sandeep Swargam Khateef Riazunnisa Thummala Chandrasekhar Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach Results in Chemistry STAT3 CRC Glide Docking MD simulations |
| title | Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach |
| title_full | Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach |
| title_fullStr | Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach |
| title_full_unstemmed | Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach |
| title_short | Identification of a natural antagonist for signal transducer and activator of transcription 3 (STAT3) by computational approach |
| title_sort | identification of a natural antagonist for signal transducer and activator of transcription 3 stat3 by computational approach |
| topic | STAT3 CRC Glide Docking MD simulations |
| url | http://www.sciencedirect.com/science/article/pii/S2211715623002096 |
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