Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents
Abstract Background Lung cancer has been reported to be among the leading cancer cases in the world. It was also reported to have caused a lot of death every year and accounted for about one-third of the whole cancer deaths in the globe. The main subset of lung cancers that accounts for about 85% of...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-12-01
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| Series: | Beni-Suef University Journal of Basic and Applied Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43088-020-00077-5 |
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| author | Muhammad Tukur Ibrahim Adamu Uzairu Sani Uba Gideon Adamu Shallangwa |
| author_facet | Muhammad Tukur Ibrahim Adamu Uzairu Sani Uba Gideon Adamu Shallangwa |
| author_sort | Muhammad Tukur Ibrahim |
| collection | DOAJ |
| description | Abstract Background Lung cancer has been reported to be among the leading cancer cases in the world. It was also reported to have caused a lot of death every year and accounted for about one-third of the whole cancer deaths in the globe. The main subset of lung cancers that accounts for about 85% of the problems of lung cancer raised above was non-small cell lung cancer (NSCLC). The most common cause of NSCLCs that mostly affects women and cigarette smokers was recognized to be overexpression of epidermal growth factor receptor tyrosine kinase (EGFR TK). Results Five models on thirty five (35) NSCLC therapeutic agents were developed via quantitative structure-activity relationship (QSAR) technique. The best model among them was selected and reported due to its fitness statistically with the following validation parameters: R 2 of 0.8764, R 2 adj of 0.8370, Q cv 2 of 0.7655, R 2 test of 0.7024, and LOF of 0.3312. Molecular docking was used to elucidate the mode of binding interactions between the thirty five (35) NSCLC therapeutic agents and the binding pose of EGFR tyrosine kinase receptor (3IKA) in this research. Compound 29 was recognized to have the most excellent binding affinity of − 8.8 kcal/mol among others. The drug-likeness and pharmacokinetic properties of all the NSCLC therapeutic agents were predicted using SWISSADME, and none among the molecules under investigation violated more than the permissible limit of the conditions stated by Lipinski’s RO5 filters. Five hit compounds were identified using molecular docking virtual screening. The five (5) hit compounds were further screened and identified compound 16 and 27 as excellent among them using their pharmacokinetic profiles and drug-likeness properties. Conclusion QSAR technique was used to build five models on thirty five (35) NSCLC therapeutic agents. The best model among them was reported because it is statistically significant with good validation parameters. The molecular docking result has identified five (5) hit compounds. The most common amino acid residues to all hit compounds under investigation were Glu762, Leu718, Lys745, and Val726 which might be responsible for the higher inhibitory activities/binding affinities of the compounds under investigation. Furthermore, these five (5) hit compounds were further subjected to drug-likeness and pharmacokinetic properties prediction to determine which among them have the best pharmacokinetic profile. Compounds 16 and 27 among the hit compounds were observed to have high chance of passive absorption by the gastrointestinal tract while the other three have low tendency of passive absorption. More so, only compounds 16 and 27 have higher bioavailability scores, and none of the two have more than one violation of the RO5 criteria. The cause of efficiency of compounds 16 and 27 might be as a result of good pharmacokinetic profiles and drug-likeness properties possessed by the molecules when compared to other hit compounds. |
| first_indexed | 2024-12-17T00:38:20Z |
| format | Article |
| id | doaj.art-20d8941bdfc041e1b47bfcba033cdd43 |
| institution | Directory Open Access Journal |
| issn | 2314-8543 |
| language | English |
| last_indexed | 2024-12-17T00:38:20Z |
| publishDate | 2020-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Beni-Suef University Journal of Basic and Applied Sciences |
| spelling | doaj.art-20d8941bdfc041e1b47bfcba033cdd432022-12-21T22:10:05ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432020-12-019111410.1186/s43088-020-00077-5Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agentsMuhammad Tukur Ibrahim0Adamu Uzairu1Sani Uba2Gideon Adamu Shallangwa3Department of Chemistry, Ahmadu Bello UniversityDepartment of Chemistry, Ahmadu Bello UniversityDepartment of Chemistry, Ahmadu Bello UniversityDepartment of Chemistry, Ahmadu Bello UniversityAbstract Background Lung cancer has been reported to be among the leading cancer cases in the world. It was also reported to have caused a lot of death every year and accounted for about one-third of the whole cancer deaths in the globe. The main subset of lung cancers that accounts for about 85% of the problems of lung cancer raised above was non-small cell lung cancer (NSCLC). The most common cause of NSCLCs that mostly affects women and cigarette smokers was recognized to be overexpression of epidermal growth factor receptor tyrosine kinase (EGFR TK). Results Five models on thirty five (35) NSCLC therapeutic agents were developed via quantitative structure-activity relationship (QSAR) technique. The best model among them was selected and reported due to its fitness statistically with the following validation parameters: R 2 of 0.8764, R 2 adj of 0.8370, Q cv 2 of 0.7655, R 2 test of 0.7024, and LOF of 0.3312. Molecular docking was used to elucidate the mode of binding interactions between the thirty five (35) NSCLC therapeutic agents and the binding pose of EGFR tyrosine kinase receptor (3IKA) in this research. Compound 29 was recognized to have the most excellent binding affinity of − 8.8 kcal/mol among others. The drug-likeness and pharmacokinetic properties of all the NSCLC therapeutic agents were predicted using SWISSADME, and none among the molecules under investigation violated more than the permissible limit of the conditions stated by Lipinski’s RO5 filters. Five hit compounds were identified using molecular docking virtual screening. The five (5) hit compounds were further screened and identified compound 16 and 27 as excellent among them using their pharmacokinetic profiles and drug-likeness properties. Conclusion QSAR technique was used to build five models on thirty five (35) NSCLC therapeutic agents. The best model among them was reported because it is statistically significant with good validation parameters. The molecular docking result has identified five (5) hit compounds. The most common amino acid residues to all hit compounds under investigation were Glu762, Leu718, Lys745, and Val726 which might be responsible for the higher inhibitory activities/binding affinities of the compounds under investigation. Furthermore, these five (5) hit compounds were further subjected to drug-likeness and pharmacokinetic properties prediction to determine which among them have the best pharmacokinetic profile. Compounds 16 and 27 among the hit compounds were observed to have high chance of passive absorption by the gastrointestinal tract while the other three have low tendency of passive absorption. More so, only compounds 16 and 27 have higher bioavailability scores, and none of the two have more than one violation of the RO5 criteria. The cause of efficiency of compounds 16 and 27 might be as a result of good pharmacokinetic profiles and drug-likeness properties possessed by the molecules when compared to other hit compounds.https://doi.org/10.1186/s43088-020-00077-5QSARNSCLCIn silicoSWISSADMEApplicability domain |
| spellingShingle | Muhammad Tukur Ibrahim Adamu Uzairu Sani Uba Gideon Adamu Shallangwa Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents Beni-Suef University Journal of Basic and Applied Sciences QSAR NSCLC In silico SWISSADME Applicability domain |
| title | Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents |
| title_full | Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents |
| title_fullStr | Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents |
| title_full_unstemmed | Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents |
| title_short | Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents |
| title_sort | quantitative structure activity relationship molecular docking drug likeness and pharmacokinetic studies of some non small cell lung cancer therapeutic agents |
| topic | QSAR NSCLC In silico SWISSADME Applicability domain |
| url | https://doi.org/10.1186/s43088-020-00077-5 |
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