Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach.
The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabo...
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Public Library of Science (PLoS)
2024-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296010&type=printable |
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| author | H G Gowtham Prasanna D Revanasiddappa Mahadevamurthy Murali Sudarshana Brijesh Singh M R Abhilash Sushma Pradeep Chandan Shivamallu Raghu Ram Achar Ekaterina Silina Victor Stupin Natalia Manturova Ali A Shati Mohammad Y Alfaifi Serag Eldin I Elbehairi Shiva Prasad Kollur |
| author_facet | H G Gowtham Prasanna D Revanasiddappa Mahadevamurthy Murali Sudarshana Brijesh Singh M R Abhilash Sushma Pradeep Chandan Shivamallu Raghu Ram Achar Ekaterina Silina Victor Stupin Natalia Manturova Ali A Shati Mohammad Y Alfaifi Serag Eldin I Elbehairi Shiva Prasad Kollur |
| author_sort | H G Gowtham |
| collection | DOAJ |
| description | The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential. |
| format | Article |
| id | doaj-art-748d274a94e24c88ad5a6a7e6ecbf97d |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-748d274a94e24c88ad5a6a7e6ecbf97d2025-08-20T02:10:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029601010.1371/journal.pone.0296010Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach.H G GowthamPrasanna D RevanasiddappaMahadevamurthy MuraliSudarshana Brijesh SinghM R AbhilashSushma PradeepChandan ShivamalluRaghu Ram AcharEkaterina SilinaVictor StupinNatalia ManturovaAli A ShatiMohammad Y AlfaifiSerag Eldin I ElbehairiShiva Prasad KollurThe present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296010&type=printable |
| spellingShingle | H G Gowtham Prasanna D Revanasiddappa Mahadevamurthy Murali Sudarshana Brijesh Singh M R Abhilash Sushma Pradeep Chandan Shivamallu Raghu Ram Achar Ekaterina Silina Victor Stupin Natalia Manturova Ali A Shati Mohammad Y Alfaifi Serag Eldin I Elbehairi Shiva Prasad Kollur Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. PLoS ONE |
| title | Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. |
| title_full | Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. |
| title_fullStr | Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. |
| title_full_unstemmed | Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. |
| title_short | Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach. |
| title_sort | secondary metabolites of trichoderma spp as egfr tyrosine kinase inhibitors evaluation of anticancer efficacy through computational approach |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0296010&type=printable |
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