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Breast cancer is the most common cancer among women worldwide. Breast cancer is caused by the overexpression of genes that facilitate breast cell proliferation. Estrogen receptor alpha (ER α) mediation is mostly responsible for the development of malignant tumors by regulating the transcription of various genes as a transcription factor. ER α is regarded as an important receptor for the proliferation of this disease and its inhibition is necessary for the treatment of breast cancer. In our study, the aim is to find out potential inhibitors for ER α by docking 100 anticancer constituents of different halogen-based derivatives against ER α. Among the 100 X -based derivatives, 20 ligands were selected based on the interaction energy ranging from − 6.7 kcal/mol to − 8.2 kcal/mol and lower values of inhibition constant (0.92–11.77 μ mol). We have performed a comprehensive analysis of five most popular ligands (L17, L57, L61, L67, and L70) among these 20 selected derivatives. The interaction analysis is mainly stabilized by making different interactions including hydrogen bonding, hydrophobic, electrostatic, and halogen bonding with the active site of ER α. A quantum study based on frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and global chemical reactivity descriptor (GCRD) is carried out to explore the structural chemistry of our most popular ligands which indicates that they are quite reactive and kinetically stable. Additionally, we also assess the ADMET profiles to predict the toxicity and drug-likeness of our lead compounds. Our selected ligands have the highest absorption and good clearance rate and have no AMES toxicity, skin sensitization, and hepatotoxicity. Molecular dynamics simulations were run to check the conformational stability of apo form of ER α and complex state, at 60-ns time scale. The molecular dynamics simulations are based on the plots of RMSD, RMSF, R g , SASA, and the number of H-bonds. The results of RMSD and RMSF showed that the lead compounds L17, L57, L61, L67, and L70 are most stable and have no significant residual fluctuations and deviation. The analysis of the plots of R g , SASA, and the number of H-bonds revealed that the complexes L17, L57, and L70 are most stable. So, the lead anticancer compounds L17, L57, L61, L67, and L70 are the most promising inhibitors against ER α of breast cancer. The comprehensive analysis of all studied parameters highlighted that our selected ligands have great potential to inhibit ER α. So, it can be concluded that the selected halogen-based derivatives can promote rational drug design for the target therapies of ER α of breast cancer. We employed triple hybrid techniques (molecular docking, dynamics and quantum chemical) to screen 100 halogen-based derivatives for potential therapeutic candidates against ER α of breast cancer. [ABSTRACT FROM AUTHOR]

The ongoing eruption of the COVID-19 pandemic instigated by severe-acute-respiratory-syndrome-coronavirus 2 (SARS-CoV-2) has produce enormous damage to the world. The need of the hour is to stop this pandemic by inhibiting the main protease (MPro) of SARS-CoV-2, which is primarily involved in viral replication. Our study aims to find potential inhibitors for MPro by docking marine fungi-based 90 antiviral compounds against SARS-CoV-2. Among these, 11 antiviral compounds (obeying Lipinski RO5) are selected from 90 docked antiviral compounds on the basis of binding energy range (− 6.4 kcal/mol to − 9 kcal/mol) and low inhibition constant values (0.23 μ M to 2.5 μ M) as compared with remdesivir (reference compound) toward MPro of SARS-CoV-2. Tryptoquivaline F, arisugacin B, and arisugacin A antiviral compounds exhibited effective hydrogen and hydrophobic (alkyl, π -alkyl, and π -anion) interactions and are expected to be potential protease inhibitors. Drug-likeness of these lead compounds are elaborated by boiled-egg and bioavailability radar map. The toxicity profile showed that the lead compounds L1, L2, and L3 have no AMES toxicity, skin sensitization, and cardiac toxicity. The RMSD graph proposed that all the complexes, i.e. L1, L2, and L3 are in the adequate RMSD range with the average value of 2.1 Å. All the complex systems of L1, L2, and L3 showed fluctuations in the acceptable RMSF range of 1.5 Å to 3 Å. The molecular dynamics simulation proved the stability of docked complexes L1, L2, and L3 in the binding pocket of main protease. The average hydrogen count of all complexes is L1 = 6 9. 5 , L2 = 6 7. 7 , and L3 = 6 8. 6 H-bonds. The complexes L1-MPro, L2-MPro, and L3-MPro have an average value of R g as 22.44 Å, 22.63 Å, and 22.50 Å, respectively. The lead compounds L1 (tryptoquivaline F), L2 (arisugacin b), and l3 (arisugacin A) in this study are the most promising inhibitors of SARS-CoV-2 main protease MPro, which are not reported in ealier studies. Our findings will evoke the scientific interest for their further in vitro and in vivo experimental studies. The marine fungi-based 90 antiviral agents from different chemical classes were screened against MPro of SARS-CoV-2. The lead compounds L1 (Tryptoquivaline F), L2 (Arisugacin B), L3 (Arisugacin A) in current study are the most promising inhibitors of SARS-CoV-2 main protease MPro. [ABSTRACT FROM AUTHOR]