Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives
Abstract The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlati...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-10-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-43175-x |
| _version_ | 1797577004535513088 |
|---|---|
| author | Shopnil Akash Imren Bayıl Md. Saddam Hossain Md. Rezaul Islam Md. Eram Hosen Amare Bitew Mekonnen Hiba-Allah Nafidi Yousef A. Bin Jardan Mohammed Bourhia Talha Bin Emran |
| author_facet | Shopnil Akash Imren Bayıl Md. Saddam Hossain Md. Rezaul Islam Md. Eram Hosen Amare Bitew Mekonnen Hiba-Allah Nafidi Yousef A. Bin Jardan Mohammed Bourhia Talha Bin Emran |
| author_sort | Shopnil Akash |
| collection | DOAJ |
| description | Abstract The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4′-O-Rhamnoside and Apigenin-4′-Alpha-l-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-d-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of − 7.5 kcal/mol to − 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings. |
| first_indexed | 2024-03-10T22:02:46Z |
| format | Article |
| id | doaj.art-d7f7ff281ead4730b5c03d1c6e1c0771 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T22:02:46Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d7f7ff281ead4730b5c03d1c6e1c07712023-11-19T12:55:46ZengNature PortfolioScientific Reports2045-23222023-10-0113112210.1038/s41598-023-43175-xNovel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivativesShopnil Akash0Imren Bayıl1Md. Saddam Hossain2Md. Rezaul Islam3Md. Eram Hosen4Amare Bitew Mekonnen5Hiba-Allah Nafidi6Yousef A. Bin Jardan7Mohammed Bourhia8Talha Bin Emran9Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International UniversityDepartment of Bioinformatics and Computational Biology, Gaziantep UniversityDepartment of Biomedical Engineering, Faculty of Engineering & Technology, Islamic UniversityDepartment of Pharmacy, Faculty of Allied Health Sciences, Daffodil International UniversityProfessor Joarder DNA and Chromosome Research Laboratory, Department of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Biology, Bahir Dar UniversityDepartment of Food Science, Faculty of Agricultural and Food Sciences, Laval UniversityDepartment of Pharmaceutics, College of Pharmacy, King Saud UniversityDepartment of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr UniversityDepartment of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown UniversityAbstract The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4′-O-Rhamnoside and Apigenin-4′-Alpha-l-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-d-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of − 7.5 kcal/mol to − 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings.https://doi.org/10.1038/s41598-023-43175-x |
| spellingShingle | Shopnil Akash Imren Bayıl Md. Saddam Hossain Md. Rezaul Islam Md. Eram Hosen Amare Bitew Mekonnen Hiba-Allah Nafidi Yousef A. Bin Jardan Mohammed Bourhia Talha Bin Emran Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives Scientific Reports |
| title | Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives |
| title_full | Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives |
| title_fullStr | Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives |
| title_full_unstemmed | Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives |
| title_short | Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives |
| title_sort | novel computational and drug design strategies for inhibition of human papillomavirus associated cervical cancer and dna polymerase theta receptor by apigenin derivatives |
| url | https://doi.org/10.1038/s41598-023-43175-x |
| work_keys_str_mv | AT shopnilakash novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT imrenbayıl novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT mdsaddamhossain novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT mdrezaulislam novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT mderamhosen novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT amarebitewmekonnen novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT hibaallahnafidi novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT yousefabinjardan novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT mohammedbourhia novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives AT talhabinemran novelcomputationalanddrugdesignstrategiesforinhibitionofhumanpapillomavirusassociatedcervicalcanceranddnapolymerasethetareceptorbyapigeninderivatives |