Investigations of Electronic, Structural, and In Silico Anticancer Potential of Persuasive Phytoestrogenic Isoflavene-Based Mannich Bases
-
Published:2023-08-06
Issue:15
Volume:28
Page:5911
-
ISSN:1420-3049
-
Container-title:Molecules
-
language:en
-
Short-container-title:Molecules
Author:
Mutahir Sadaf12ORCID, Khan Muhammad Asim12ORCID, Mushtaq Maryam2, Deng Haishan3, Naglah Ahmed M.4, Almehizia Abdulrahman A.4ORCID, Al-Omar Mohamed A.4ORCID, Alrayes Faris Ibrahim4, Kalmouch Atef5, El-Mowafi Shaima A.5, Refat Moamen S.6ORCID
Affiliation:
1. School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000, China 2. Department of Chemistry, University of Sialkot, Sialkot 51300, Pakistan 3. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China 4. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia 5. Peptide Chemistry Department, Chemical Industries Research Institute, National Research Centre, Cairo 12622, Egypt 6. Department of Chemistry, Faculty of Science, Port Said University, Port Said 42526, Egypt
Abstract
Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.
Funder
King Saud University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference44 articles.
1. Anticancer activity of Thymol: A literature-based review and docking study with Emphasis on its anticancer mechanisms;Islam;IUBMB Life,2019 2. Arshad, R., Khan, M.A., Mutahir, S., Hussain, S., Al-Hazmi, G.H., and Refat, M.S. (2022). DFT, Molecular Docking and ADME Studies of Thiazolidinones as Tyrosinase Inhibitors. Polycycl. Aromat. Compd., 1–16. 3. Mutahir, S., Khan, M.A., Naglah, A.M., Al-Omar, M.A., Almehizia, A.A., Huwaimel, B., Abouzied, A.S., Alharbi, A.S., and Refat, M.S. (2023). Structural Characterization and Molecular Docking Screening of Most Potent 1,2,4-Triazine Sulfonamide Derivatives as Anti-Cancer Agents. Crystals, 13. 4. A concise review on cancer treatment methods and delivery systems;Bidram;J. Drug Deliv. Sci. Technol.,2019 5. Debela, D.T., Muzazu, S.G., Heraro, K.D., Ndalama, M.T., Mesele, B.W., Haile, D.C., Kitui, S.K., and Manyazewal, T. (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med., 9.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|