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Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed relatively highest βtot (69.89 x 10–31 esu), highest αave (3.18 x 10–23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells. [ABSTRACT FROM AUTHOR]

Breast cancer (Bca) causes the highest rate of mortality in females owing to the out-of-control cell division in breast cells. In this work, we perform an in-silico screening based on molecular docking and molecular dynamic of curcumin derivatives against ERα. In this study, we carry out, molecular docking of fifty (50) curcumin derivatives having anticancer potential by using virtual screening tools. Ten (10) ligands were selected based on binding energy ranged from (-7.4 kcal/mol to -9 kcal/mol), lower values of inhibition constant (0.23µmol to 3.59µmol), and visualisation of intermolecular interactions. Additionally, we also assess ADMET properties of selected ligands for prediction of their toxicity and drug-likeness. The molecular dynamic simulations (MD) including RMSD, RMSF, Rg, SASA, number of H-bonds and MM-PBSA binding free energy results showed that ligand L2 and L8 bind to estrogen protein ERα more proficiently with good stability over 120 ns. These results suggest lead anticancer compounds L2 (Salicylidenecurcumin) and L8 (Curcumin difluorinated) are the most promising inhibitor against ERα of Bca with ∆Gbind values of (-2.939 and -4.369) kcal/mol. we expect that our findings will evoke the scientific community to further do in-vitro and in-vivo investigations for screened curcumin derivatives against ERα of Bca. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, which causes COVID-19 disease, has proven to be a disastrous pandemic due to its contagious nature. This study has been planned to theoretically explore some antidotes against this virus from natural compounds. A total of 150 compounds from the shogaol class and shogaol derivatives (SDs) have been screened whereas 50 among those, which obeyed Lipinski's Rule of Five (Ro5), have further been investigated using molecular docking techniques. Furthermore, reference antiviral drug chloroquine (ChQ) and Co-Crystallized inhibitor have also been studied against Mpro of SARS-CoV-2 for comparing the potential of our docked ligands. Surprisingly, 78% of our docked ligands have shown binding energies and inhibition constants lower than ChQ and all ligands showed these values lower than an inhibitor. We further visualized the nature of intermolecular interactions for the best docked six ligands, which have shown higher binding affinities. We have also assessed ADMET properties for three ligands that displayed visually the best intermolecular interactions. Quantum analysis of three selected ligands L4, L5, and L9 has proved their reactivity and kinetic stability. Moreover, molecular dynamic simulations over 60 ns have been run for free Mpro and its selected three ligand-protein complexes for evaluating conformational stability and residual flexibility of docked complexes. Furthermore, 100 ns the MD simulations have been performed for two ligand complexes L4, L5 (with negative binding free energy), and inhibitor. Available parameters suggest stable complexes for our ligands and could be active drugs against SARS-CoV-2 in near future. A total of 50 shogaol derivatives (SDs) which obeyed Lipinski's rule of five (Ro5) have been investigated using molecular docking and dynamic techniques. We have also assessed intermolecular interactions, ADMET properties, quantum chemical analysis for the best complexes. [ABSTRACT FROM AUTHOR]

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n -butyl (1 , 3), methyl (2 , 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1 , 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1–4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = −3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score −5.2957). Further, the docking analysis of the HL and 1–4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2). [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]

Eight new oxadiazole derivatives were designed then geometries for ground state were optimized through Density Functional Theory (DFT) at B3LYP/6-31G** level. Single electron transfer mechanism has been studied to understand the antioxidant ability of the oxadiazole derivatives. Then molecular electrostatic potential and quantitative structure–activity relationship (QSAR) was probed. Additionally, we shed light on different molecular descriptors, e.g., electrophilicity(ω), electronegativity(χ), electrophilicity indices(ωi), hardness(η), softness(S) and chemical potential(μ).The smaller value of ionization potential for 5a is showing that it might be efficient antioxidant candidate. The electrophilic reactive sites in 2a, 3a, 4a , 5a and 7a derivatives might be a good choice for reactivity that would be advantageous to improve the biological activity. The polar surface area of 3a , 4a and 5a derivatives was found < 60 A2 which is enlightening that these drugs might be suitable as orally active and for brain penetration. First-principles calculations and molecular docking results revealed that 5a would lead to superior antioxidant activity. [ABSTRACT FROM AUTHOR]

The present investigation uses a dual approach to study the copper (II) complex [Cu(phen)3]. (ClO4)2.HL.CH3CN (1) and its cationic complex‐ [Cu(II)(phen)3]2+ (1 a), where, HL = 4‐Bromo‐2((Z) ‐(naphthalene‐4‐ylimino)methyl)phenol, phen=1,10‐phenanthroline. The complex (1) crystallized in the triclinic system of the space group P‐1 with two molecules in the unit cell and reveals a distorted octahedral geometry. Inspiring by recent developments to find a potential inhibitor for the COVID‐19 virus, we have also performed molecular docking study of [Cu(phen)3]+2 to see if our novel complex shows an affinity for the main protease (Mpro) of COVID‐19 spike protein. Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be −8.400 kcal/mol and 0.661 μM, respectively, for the best‐docked confirmation of [Cu(II)(Phen)3]+2 complex with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of [Cu(II)(Phen)3]+2 complex is found to be better than recently docking results of chloroquine (−6.293 kcal/mol), hydroxychloroquine (−5.573 kcal/mol) and remdesivir (−6.352 kcal/mol) with Mpro protein. Thus, we believe the broad‐spectrum functional properties of our complex will provoke not only the interest of material chemists in materials designing but also incite the drug designing community. [ABSTRACT FROM AUTHOR]

Three novel pyrimidine based bis-uracil derivatives 1–3 were synthesized by the condensation reaction of 2-hydroxynaphthaldehyde with 6-amino-1,3-dimethylpyrimidine-2,-4(1H, 3H)-dione; 6-amino-1, 3-diethylpyrimidine-2,-4(1H, 3H)-dione, and 6-amino-1,-ethyl-3-methylpyrimidine-2,-4(1H, 3H)-dione, respectively and structurally characterized. The preliminary test of compounds was evaluated by SwissADME that can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavors. Antimicrobial, photoluminescence, and molecular docking of compounds were also studied. The kinetic and thermal stabilities along with intramolecular charge transfer characters were obtained for compounds using frontier molecular orbitals, electrostatic potential diagrams as well as their orbital energies. Additionally, we applied state-of-art computational methods to assess the linear and nonlinear optical (NLO) properties of compounds at M06/6-311G** levels of theory. The third-order NLO properties of 1–3 were observed larger as compared to the standard indicating the considerable NLO character of all molecules, which may render the above derivatives as efficient candidates for NLO device fabrications. [ABSTRACT FROM AUTHOR]

The phytochemicals can play complementary medicine compared to synthetic drugs considering their natural origin, safety, and low cost. Phytochemicals hold a key position for the expansion of drug development against corona viruses and need better consideration to the agents that have already been shown to display effective activity against various strains of corona viruses. In this study, we performed molecular docking studies on potential forty seven phytochemicals which are SARS-CoV-1 Mpro inhibitors to identify potential candidate against the main proteins of SARS-CoV-2. In Silico Molecular docking studies revealed that phytochemicals 16 (Broussoflavan A), 22 (Dieckol), 31 (Hygromycin B), 45 (Sinigrin) and 46 (Theaflavin-3,3′-digallate) exhibited excellent SARS-CoV-2 Mpro inhibitors. Furthermore, supported by Molecular dynamics (MD) simulation analysis such as Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of gyration (Rg) and H-bond interaction analysis. We expect that our findings will provide designing principles for new corona virus strains and establish important frameworks for the future development of antiviral drugs. [ABSTRACT FROM AUTHOR]

The Covid-19 pandemics caused by SARS-CoV-19, and the inadequacy of targeted medications, compelled scientists to seek new antiviral drugs. We present our current understanding of plant extracts containing polyphenols that inhibit Covid-19. Natural phytochemicals (polyphenols) derived from plants have the potential to establish research using extracts and/or individual compounds in the treatment and prevention of coronavirus. The polyphenolic drugs (antivirus) capable of inhibiting the coronavirus protein, that are vital for infection and virus replication. The benefit of phytochemicals is that they promote patient well-being while causing minimal side effects. To understand the antiviral behavior of isolated phytochemicals 1 – 6 , various molecular descriptors, molecular electrostatic potential (MEP), and frontier molecular orbitals (FMO) were investigated. A systematic analysis of isolated phytochemicals was accomplished then molecular descriptors, docking score, active sites, and FMOs energies were compared to the commonly used drugs recently to treat COVID19, namely favipiravir, remdesivir dexamethasone and hydroxychloroquine. Using a molecular docking technique, we demonstrate for the first time that these plant phytochemicals can be inhibited by the core protease (6LU7) protein of COVID19. [ABSTRACT FROM AUTHOR]

Bioassay guided fractionation of Pistacia integerrima crude methanolic extract gave Pistacide-A (1) and Pistacide-B (2), along with ten known phytochemicals (3 – 12). Biochemical analysis of crude plant extract, in-vitro and in-silico carbonic anhydrase inhibitory potential of newly isolated compounds Pistacide-A (1) and Pistacide-B (2) were performed. The cytotoxicity of extract in methanol, ethylacetate and n -butanol against Artemia salina brine-shrimp was 34.98 g/ml, 160.81 g/ml, and 135.77 g/ml, respectively. The significant antimicrobial activity was exhibited by crude, ethyl acetate, and n -butanol fractions. Compounds 1 (IC 50 = 6.51 ± 0.42 mM) and 2 (IC 50 = 2.85 ± 0.09 mM) showed good carbonic anhydrase inhibition compared with standard zonisamide drug (IC 50 = 1.87 ± 0.003 mM). In addition, we have also clarified the electronic properties, absorption wavelengths, molecular electrostatic potential and Hirshfeld analysis by first-principles studies. The coherent intra-molecular charge transfer was seen from occupied to unoccupied molecular orbitals. The absorption wavelengths calculated at time dependent B3LYP/6-31G** level in methanol provided excellent accord with the experimental evidence. Molecular docking score revealed that Pistacide-B would be an efficient drug than its other counterpart that is rational to the experimental data. [ABSTRACT FROM AUTHOR]

The exploration of natural sources of antioxidant phytochemicals for human use with little toxicity gained worldwide attention. The preliminary screening of Malva sylvestris extracts revealed that its phytochemicals such as polyphenols, flavonoids and tannins, have high therapeutic potential. The total phenolic/flavonoids compounds of Malva sylvestris were extracted and isolated using bioassay guidelines, as well as in-silico studies. The extracts radical scavenging activity was further investigated using 1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radical bioassays. The antioxidant potentials of various fractions were compared to standard antioxidants such as ascorbic acid and quercetin. The dichloromethane extracts of Malva sylvestris exhibited the antiradical activity against DPPH and NO with radical scavenging activities (RSA) of 88.52 and 91.05% with IC 50 values 22.11 and 19.01 µg/mL respectively. Bio guided isolation form the dichloromethane sub fractions that afforded twelve phytochemicals. Furthermore, the frontier molecular orbitals (FMO), several molecular descriptors, electron affinity, ionization potential and molecular electrostatic potential (MEP) have been discussed to probe the active sites of various phytochemicals. A systematic study of isolated drugs was conducted, as well as docking, frontier molecular orbitals energies, active sites and molecular descriptors were compared with drugs currently used against COVID19 namely, dexamethasone, hydroxychloroquine, favipiravir and remdesivir. For the first time, through molecular docking approach, the inhibitions of these plant phytochemicals with NADPH were recorded to show antioxidant behavior and to explore anti-SARS-CoV-2 using core protease (6LU7) protein. [ABSTRACT FROM AUTHOR]

The methanolic extract along its various fractions Abutilon pakistanicum were analyzed to find total phenolic, flavonoids contents followed by antioxidant and α-glucosidase inhibitions of isolated pure constituents. The total content of phenolics and flavonoids was consistently higher in CH 2 Cl 2 (54.89 and 56.06 mg/g extract respectively) compared with n -hexane, ethyl acetate, n -butanol and H 2 O portions (ranging between 37.81–54.89 and 38.11–56.06 mg/g extract). In order to determine active biological ingredients from CH 2 Cl 2 subportions, extensive advanced chrotapographic separation methods resulted isolation of new flavonoid glycosides namely abutilins C-D (1 – 2). The structures of these constituents were interpreted by spectroscopic data including FAB-MS, ESI-MS, 1D and 2D-NMR experiments. Both flavonoid (1 – 2) were evaluated against antioxidant and α-glucosidase inhibitory assay. The antioxidant potential of dichloromethane extract and abutilins C-D (1 – 2) were determined using DPPH and nitric oxide radial scavenging assays. The abutilins C displayed significant inhibition, with IC 50 values 41.66 (DPPH), 39.04 (NOS) µ g/mL, using positive control ascorbic acid and quercetin respectively. Inhibitory effects of flavonoids against enzyme α-glucosidase were also investigated and abutilins C showed significant activity with IC 50 values 8.27 µg/mL compared with positive control ascarbose (IC 50 , 5.92 µg/mL). Abutilins C can serve dual inhibitors as antioxidant agent and to treat α-glucosidase associated diseases. Phytochemicals geometries i.e ground state were optimized by density functional theory (DFT) B3LYP/TZ2P to understand the electronic properties of the studied compounds. The ground state geometries of abutilin_C, abutilin_D and reference compounds were optimized by DFT then various electronic properties were explored. Moreover, we have also investigated the global molecular descriptors, molecular electrostatic potential, Hirshfeld analysis and molecular docking by quantum chemical calculations. [ABSTRACT FROM AUTHOR]

• Marine sponge derivatives are studied as an anticancer agent for breast cancer cells. • Residues involved in this interaction are characterized using molecular docking studies. • Molecular dynamic (MD) simulations over 120 nanoseconds were run. • MM/PBSA analysis are studied to mimic complex stability in aqueous environment. • Importantly, several screening filters were applied by assesing their ADMET properties. • The current in-silico findings are highly ecourging for in-vitro and/or wet lab analysis. The oceans cover about 96.5 % of all the Earth's water and are virtually unexploited resources for novel drug discovery. Members of almost every phylum are found in the oceans, whereas twelve phyla are exclusively marine. A very limited fraction of marine compounds have been tested in clinically relevant bioassays. Higher resistance of pathogenic microorganisms to antibiotics and disease cells to antitumor medications requires a new phase of novel medicines. The study aims to explore the potential of marine sponges as natural inhibitors for breast cancer therapy using an optimized in-silico technique. We perform in -silico analysis for around two hundred and seventy-two (272) marine sponge compounds against ERα of breast cancer using molecular docking and dynamics techniques. The results of the current study were carefully used to screen the compounds with the potential to inhibit ERα of breast cancer. For instance, molecular docking analysis reveals that six top-hit selected ligands L1 (Di(IH-indol-3-yl) methanone), L2 (1,2-Bis (1H-indol-3-yl)ethane-1,2‑dione), L3 2-(4-benzylpiperidin-1-yl)1-(1H-indol-3-yl)ethenone), L4 (5H-Pyrido[4,3- b ]carbazole-5,11(6H)‑dione), L5 (4H-pyrido[2,3,4-K l ]acridine-4-one), and L6 15-methyl-2, 12,15-triazapentacyclo[11.7.1.03,8,09,21.014,19]henicosa-1,3,5,7,9(21),10,12,14(19),16-nonaene-18,20‑dione) show docking scores values ranging from -9.2 kcal/mole to -9.5 kcal/mol in comparison to reference drug inhibitor -8.6 kcal/mole to -9.5 kcal/mol. For comparison purposes, reference drug candidates like tamoxifen, ospemifene, and quinestrol have been studied under the same in -silico methodology. The ligand-protein interactions displayed various types of intermolecular interactions, including hydrogen bond formationand hydrophobic and π-π stacking interactions towards the active site of the protein. Explicit molecular dynamic (MD) simulations for 120 ns were executed to mimic the in-vitro aqueous environment and stability pattern of ligand-protein complexes through RMSD, RMSF, Rg, SASA, and intermolecular H-bond. Furthermore, MM/PBSA calculation also confirmed the good binding free energy (Δ G b i n d ) of L1 (-22.63 kcal/mol), L2 (-13.81 kcal/mol), L3 (-19.23 kcal/mol), L4 (-24.50 kcal/mol), L5 (-14.44 kcal/mol), and L6 (-8.16 kcal/mol) towards ERα (1 gwr). Additionally, the ADMET prediction of top-hit ligands was observed to have good drug-likeness criteria (Lipinski RO5) and pharmacokinetic properties. The in-silico approach identified ligands L1, L2, L3, L4, L5, and L6 as a promising inhibitor of ERα of breast cancer, suggesting in vivo/in vitro studies to investigate their inhibitory potentials further. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferrocene and its derivatives are vital class of organometallic compounds having extensive biological activities. Six novel ferrocene-based thiosemicarbazones have been synthesized through the condensation reaction of acetyl ferrocene with differently substituted thiosemicarbazide. Furthermore, we used state-of-the-art computational docking approach to explore the theoretical aspects for possible antiviral potential of our synthesized compounds. All the six compounds were docked with Mpro protein of SARS-CoV-2, which is very crucial protein for viral replication. Among the six derivatives, compounds 2 and 4 showed higher binding affinities with binding energy of − 6.7 and − 6.9 kcal/mol, respectively. The visualization of intermolecular interactions between synthesized derivatives and Mpro protein illustrated that each of compounds 2 and 4 forms two hydrogen bonds accompanied by important hydrophobic interactions. The comparison of binding affinities with some recently approved drugs like remdesivir, chloroquine and hydroxychloroquine molecules are also made. The calculated binding energies of remdesivir, chloroquine and hydroxychloroquine molecules with Mpro of COVID-19 was found to be − 7.00, − 5.20 and − 5.60 kcal/mol, respectively. The binding energy of compound 4 (− 6.9 kcal/mol) was almost equal to the remdesivir and greater than the binding energies of chloroquine and hydroxychloroquine. It is expected from the current investigation that our synthesized ferrocene-based thiosemicarbazones might have potential for drug against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This study is carried out to find novel active drug candidates which can effectively bind to key residues of main protease (Mpro) of SARSCoV-2. We performed molecular docking of fifty-seven (57) ligands from two classes: vanillylacetone and its derivatives and beta-hydroxy ketone derivatives against Mpro of SARS-CoV-2. We also docked three antiviral drugs as reference/benchmark drugs including remdesivir (RDV), chloroquine (CQ), and hydroxychloroquine (HCQ) against Mpro for comparison of inhibition tendencies of selected ligands. Binding energies of our reference drugs are as: CQ = -5.1 kcal mol-1 (with predicted inhibition constant (Ki pred) = 177 µmol), HCQ = -5.7 kcal mol-1 (Ki pred = 64.07 µmol) and RDV -6.3 kcal mol-1 (Ki pred = 13.95 µmol). We got remarkable results for our docked ligands as 79% of total ligands indicated binding energies better than CQ, 39 % better than both HCQ and CQ, and 19 % better than all reference drugs. More interestingly interaction analysis of eight best-docked ligands showed that they interacted with desired key residues of Mpro. We further selected the four best-docked ligands L1 = -6.6 kcal mol-1 (Ki pred =13.95 µmol), L6 = -7.0 kcal mol-1 (Ki pred = 7.08 µmol), L34 = -6.0 kcal mol-1 (Ki pred = 38.54 µmol), and L50 = -6.6 kcal mol-1 (Ki pred =13.95 µmol) for further analysis by quantum chemical study, molecular dynamic (MD) simulations and ADMET analysis. We have also carried out MD-simulations of six more docked ligand L2, L14, L20, L36, L46 and L48 some of which were showing weak binding affinities and some average binding affinities to check their simulation behavior. Their RMSD, RMSF and binding free energy results were also quite satisfying. We believe the current investigation will evoke the scientific community and highlights the potential of selected compounds for potential use as antiviral compounds against Mpro of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lumbrokinases are group of serine proteases. • Serine found at position 214 in lumbrokinase improved the activity of lumbrokinase. • In silico tools were used for characterization of mutant Lk-6 proteins. • Serine-Valin214 substitution were direct activation of breaking Arg561-Val562 bond. • The results of this study are step forward towards engineering smart lumbrokinases. Lumbrokinases (LKs) belong to the group serine proteases capable to prevent thrombosis through the proteolysis of both plasminogen-bound and plasminogen-free fibrin molecules. The article presents improved activity of Lumbrokinase-6 (Lk-6) by suggesting the substitution of a Serine found at position 214 (Lk-6) with three other amino acids namely Glutamic acid, Proline and Valine. To characterize the stability, enzyme-substrate interaction and improved activity of three mutant Lk-6 proteins (Lk-Glu214, Lk-Pro214, Lk-Val214) In Silico tools were utilized. Subsequently, Lk-6 wild type and three mutant proteins were subjected to structure prediction, molecular modeling, phylogeny, molecular docking and Protein-Protein Interaction (PPI) using the In Silico tools. Collection and analysis of results revealed that substituted mutation at Ser214 with Valine214 can appreciably stabilize the overall structure of Lk-6 protein and makes its interaction with plasminogen activator physically powerful for higher plasmin activation. Similarly, Serine214 to Valine214 substitution resulted the direct activation of plasmin breakage at the Arg561-Val562 bond. The Arg-Val at position 561–562 in plasminogen and its connection at catalytic site have significantly shown that the predicted residue Valine214 could be further examined through genetic engineering of Lk-6 protein. Therefore, such results are potential steps towards the engineering of smart and active Lks. [ABSTRACT FROM AUTHOR]

• Tricyclic 1 H -benzo[ f ]chromene-2-carbothioamides were synthesized as potential anticancer agents. • The cytotoxic activity was tested against MCF-7, HepG-2 and PC-3 cell lines. • Various molecular descriptors, frontier molecular orbitals, Mulliken analysis and electronic properties were studied. • The energy gaps, reactivity descriptors values and molecular docking of the target compounds were discuses. Reaction of 7‑methoxy-2-naphthol with appropriate aromatic aldehydes and 2-cyano-ethanethioamide provided the corresponding 3-amino-1-aryl-9‑methoxy-1 H -benzo[ f ]chromene-2-carbothioamide. The structures of these compounds were established on the basis of IR, 1H NMR, 13C NMR, MS data and elemental analysis. Furthermore, the anti-proliferative properties were evaluated against the human cancer cell lines MCF-7, HepG-2 and PC-3 in comparison to the positive controls Vinblastine and Doxorubicin, employing the viability assay. The obtained results confirmed that some of the tested molecules revealed strong and selective cytotoxic activities against the three cancer cell lines. Moreover, various molecular descriptors, frontier molecular orbitals (FMO), Mulliken analysis and electronic properties were studied to probe the biological activity behavior of the synthesized 1 H -benzo[ f ]chromene-2-carbothioamide derivatives. The effect of electron withdrawing groups (EWGs) and electron donating groups (EDGs) was also explored on the structural parameters and electronic nature of compounds. The energy gaps, reactivity descriptors values and molecular docking studies exhibited that some 1 H -benzo[ f ]chromene-2-carbothioamide derivatives would be active biological compounds. [ABSTRACT FROM AUTHOR]

• Antiviral constituents of Moringa oliefera were docked against non structural proteins (nsp9/10) • The structural chemistry of ligands was studied by quantum chemical calculations. • Pharmacokinetic properties were evaluated by ADMET analysis. The interactions of two crucial proteins of COVID-19 have been investigated with potential antiviral compounds from Moringa oliefera using quantum chemical, molecular docking and dynamic methods. The results of the present investigation show that ellagic acid and apigenin possess the highest binding affinities of −7.1 and −6.5 Kcal.mol-1against nsp9 and −6.9 and −7.1 Kcal.mol−1 against nsp10, respectively. The dynamic behavior of individual proteins and their respective best docked ligand–protein complexes are also studied at 30 ns timescale. Both of these compounds also show the highest intestinal absorption and total clearance rate as compared to the other compounds under present investigation without any toxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two new Schiff bases were prepared and characterized through UV/VIS, FTIR, NMR and XRD analysis. • DFT and Hirshfeld analysis were carried out to check the different theoretical aspects. • In-vitro and In-silico enzyme inhibition studies were conducted against AChE, BChE and α -glucosidases. The current project was planned to access the enzyme inhibition potential of the synthesize imines; (E)-2-(2-hydroxy-4,5-dimethoxybenzylideneamino)benzonitrile 1 and (E)-2-(((3-hydroxy-4-methylphenyl)imino)methyl)-4-methoxyphenol 2 by the reported protocol of our continuous research and also assess their theoretical function in term of in silico action. The structural characterization of imines was done through advanced techniques i.e., FTIR, 1H NMR, 13C NMR, and UV spectroscopy. Moreover, a single X-Ray diffraction technique (SCXRD) was employed for real structural identification of imines dimensions, which revealed that compound 1 has a triclinic crystal system although 2 has a monoclinic one. A 2D fingerprint plot and Hirshfeld surface analysis (HS) was employed in the crystalline assembly of compounds to check intermolecular contacts and also their degree of contributions. Both compounds were optimized by B3LYP functional mode using a certain basis set (6-31G). The practical data (XRD) and theoretical data (DFT) of both molecules were compared and found between a sound coherence. Molecular docking studies in term of in silico assessment were conducted against enzymes of the esterase and alpha-glucosidase family. The docking outputs give a forecast about compounds that could be employed as protein inhibitors against analyzed protein surfaces. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hybrid computational approach consisting of different computational methods is used. • Molecular electronic structures, and therapeutic potential of piperidine compounds are tested against SARS-CoV-2. • The molecular docking and MD simulations results reveal the significant therapeutic potential of designed compounds. • The MMPBSA analysis indicate that all the complexes possess good binding free energy at binding site of receptor. • ADMET analysis reveals that all eight ligands are efficient drug candidates for Mpro of SARS-CoV-2. In the current study, a hybrid computational approach consisting of different computational methods to explore the molecular electronic structures, bioactivity and therapeutic potential of piperidine compounds against SARS-CoV-2. The quantum chemical methods are used to study electronic structures of designed derivatives, molecular docking methods are used to see the most potential docking interactions for main protease (MPro) of SARS-CoV-2 while molecular dynamic and MMPBSA analyses are performed in bulk water solvation process to mimic real protein like aqueous environment and effectiveness of docked complexes. We designed and optimized piperidine derivatives from experimentally known precursor using quantum chemical methods. The UV–Visible, IR, molecular orbitals, molecular electrostatic plots, and global chemical reactivity descriptors are carried out which illustrate that the designed compounds are kinetically stable and reactive. The results of MD simulations and binding free energy revealed that all the complex systems possess adequate dynamic stability, and flexibility based on their RMSD, RMSF, radius of gyration, and hydrogen bond analysis. The computed net binding free energy (Δ G b i n d ) as calculated by MMPBSA method for the complexes showed the values of −4.29 kcal.mol−1 for P1, −5.52 kcal.mol−1 for P2, −6.12 kcal.mol−1 for P3, −6.35 kcal.mol−1 for P4, −5.19 kcal.mol−1 for P5, 3.09 kcal.mol−1 for P6, −6.78 kcal.mol−1 for P7, and −6.29 kcal.mol−1 for P8.The ADMET analysis further confirmed that none of among the designed ligands violates the Lipinski rule of five (RO5). The current comprehensive investigation predicts that all our designed compounds are recommended as prospective therapeutic drugs against Mpro of SARS-CoV-2 and it provokes the scientific community to further perform their in-vitro analysis. [ABSTRACT FROM AUTHOR]

Molecular modeling strategy was adopted to check the biological potential of the imine based molecules against free radical, acetylcholine esterase and butyrylcholine esterase. Three Schiff based compounds as (E)−2-(((4-bromophenyl)imino)methyl)−4-methylphenol (1), (E)−2-(((3-fluorophenyl)imino)methyl)−4-methylphenol (2) and (2E , 2E)−2-(2-(2-hydroxy-5-methylbenzylidene)hydrazono)−1,2-diphenylethanone (3) were synthesized with high yield. The synthesized compounds were characterized with the help of modern techniques such as UV, FTIR and NMR while exact structure was depicted with Single Crystal X-Ray diffraction technique which disclosed that compound 1 is orthorhombic, while 2 and 3 are monoclinic. A hybrid functional (B3LYP) method with general basis set of 6–31 G(d,p) were applied to optimize synthesized Schiff bases. The contribution of in-between molecular contacts within a crystalline assembly of compounds were studied using Hirshfeld surface analysis (HS). In order to check the ability of the synthesized compounds toward free radical and enzyme inhibition, in vitro models were used to assess the radical scavenging and enzyme inhibition potential which depicted that compound 3 showed highest potential (57.43 ± 1.0%; DPPH, 75.09 ± 1.0%; AChE and 64.47 ± 1.0%; BChE). The ADMET assessments suggested the drug like properties of the synthesized compounds. It was concluded from results (in vitro and in silico) that synthesized compound have ability to cure the disorder related to free radical and enzyme inhibition. Compound 3 was shown to be the most active compared to other compounds. [Display omitted] • Three Schiff Bases were synthesized and their characterization was done by spectroscopic techniques. • The structures of all compounds were elucidated by Single Crystal X-ray Diffraction (SCXRD). • In-Vitro free radical and enzyme inhibition potential were determined to explore their biological applications. • Molecular Docking study were done to check their in silico potential while DFT study to exhibit correlation with SCXRD data. [ABSTRACT FROM AUTHOR]

Computational designing of four different series (D-G) of thiazolidinone was done starting from different amines which was further condensed with various aldehydes. These underwent in silico molecular investigations for density functional theory (DFT), molecular docking, and absorption, distribution metabolism, excretion, and toxicity (ADMET) studies. The different electrochemical parameters of the compounds are predicted using quantum mechanical modeling approach with Gaussian. The docking software was used to dock the compounds against choosing PDB file for chickenpox, human immunodeficiency, hepatitis, and monkeypox virus as 1OSN, 1VZV, 6VLK, 1RTD, 3I7H, 3TYV, 4JU3, and 4QWO, respectively. The molecular interactions were visualized with discovery studio and maximum binding affinity was observed with D8 compounds against 4QWO (- 13.383 kcal/mol) while for compound D5 against 1VZV which was −12.713 kcal/mol. Swiss ADME web tool was used to assess the drug-likeness of the designed compounds under consideration, and it is concluded that these molecules had a drug-like structure with almost zero violations. [Display omitted] • Forty-four Thiazolidinone were proposed theoretically. • DFT and Docking studies were conducted with different software against various virus PDB files. • ADMET assessment was conducted using online available software. • Homology modeling study of the effective proteins was made. [ABSTRACT FROM AUTHOR]

[Display omitted] • A triple hybrid computational methodology is used to study modafinil drug derivatives. • Molecular docking was performed with ERα receptor to see potential interactions. • The complexes were further studied molecular dynamics simulations (120 ns). • The MMPBSA binding free energies were also calculated. • Structure-property relationship of compounds were predicted. Breast cancer (Bc a) is the prominent, most commonly detected, and the leading cause of mortality among women. Estrogen receptor alpha (ERα) is considered an important receptor for the proliferation of this disease and its blockage is necessary for the treatment of Bc a. The purpose of the current study is to design novel potential inhibitors against ERα of Bca. We designed modafinil drug derivatives using quantum chemical methods. These newly designed derivatives were put under an in-silico investigation followed by molecular docking simulation, molecular dynamics simulation, and MMPBSA analysis to find novel inhibitors of ERα. Moreover, three reference anticancer drugs; tamoxifen, raloxifene, and toremifene are also studied against ERα of Bc a. The spectroscopic and structural features of sulfoxide-based designed derivatives of modafinil drug M1 ((R)-2-(banzhydrylsulfinyl-N,N diethylacetamide) have been evaluated using different quantum chemical analyses. The findings of the current investigation demonstrate that all studied ligands exhibit the binding energy ranges (-5.3 to −5.8 Kcal/mol). The designed compounds showed effective hydrophobic (alkyl, π -alkyl, π -sigma, π -amide stacked, π - π T-shaped) interactions and hydrogen bond formation and are anticipated to be potential inhibitors against ERα. Additionally, designed derivatives have a good ADMET (absorption, distribution, metabolism, excretion, toxicity) profile and drug-likeness properties obeying RO5 without any toxicity. The stability profile of designed derivatives (M1 - M6) was further validated by molecular dynamics (MD) simulation and calculate binding free energy by the MM-PBSA approach. All ligand–protein complexes showed structural stability over the 120 ns MD simulation time. The MD simulation of the complex system was carried out by RMSD (root-mean-square deviation) of C α atoms of ERα, RMSF (root mean square fluctuations), R g (radius of gyration), SASA (solvent accessible surface area), and dynamic behavior of hydrogen bonds. The MD simulation results illustrate that RMSD for trajectories of designed derivative complexes over 120 ns are within the acceptable deviation range of ∼ 3 Å. The calculations of net binding free energy (Δ G b i n d ) between the designed derivatives and their complexes are found to be −8.50 Kcal/mol (M1) at maximum and −5.197 Kcal/mol (M3) at a minimum among all derivatives. The outcomes of our current in-silico investigation will evoke the scientific community to carry out further in vivo and in vitro studies on designed modafinil derivatives that can be potential therapeutic drug candidates against ERα. [ABSTRACT FROM AUTHOR]

The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this present study, a new quinoline compound was synthesized and characterized by spectroscopy techniques. Crystal structure was established by SCXRD analysis and data is used as an input to perform various computations. Additionally, using state-of-the-art quantum computational techniques, the geometry optimization and calculation of UV–Vis spectrum of 2F6M3CQ were performed at B3LYP/6-311G* level of theory. The optimized molecular geometric parameters as well as UV–Vis spectrum values are found to be in good agreement with their respective experimental results. The visualization of 3-D plots of FMO and MEP indicated the structure and reactivity trends of 2F6M3CQ molecule. Molecular docking methods were utilized to find the drug ability of 2F6M3CQ with Mproprotein of SARS-CoV-2. There were many intermolecular interactions between Mpro protein and 2F6M3CQ molecule which lead to good binding energy (−5.5 kcal/mol) between them which was found to be better than the binding energy of chloroquinine molecule (−4.5 kcal/mol) as studied under same docking protocols. Finally, drug likeness and ADME properties of 2F6M3CQ were also analyzed. There is no violation found for RO5 in our 2F6M3CQ compound. ADME analysis shows drug like properties of compound 2F6M3CQ which predicts that it might be a potential candidate for inhibition of SARS-CoV-2. [Display omitted] • Synthesis of functionalized 2- formyl-6-methoxy-3-carbethoxy quinoline from Vilsmeier - Haack heterocyclization of β –anilinocrotonate. • Synthesized compound was grown as single crystal in ethanol medium and SCXRD of the crystal has been done.in ethanol medium and SCXRD of the crystal has been done. • The title compound was also characterized by UV–Vis, FT- IR, and NMR Studies. • Molecular geometry of the compound was theoretically explored using DFT and compared with experimental results. • Computational methods were utilized to find the docking ability of the compound against the main protease of SARA-CoV-2. [ABSTRACT FROM AUTHOR]

• Synthesis growth and molecular interaction of organic nonlinear optical single crystals of (E)-N′-(2,3-dimethoxybenzylidene)−4-fluorobenzohydrazide (DMB-FBH) were discussed. • X-ray single-crystal diffraction analysis confirmed the structure. • Vibrational analysis and various electronic properties of the compound were studied using density functional theory (DFT) calculations. • Hirshfeld surface analyses and fingerprint plots confirmed the O...H, N...H, C...C and C...H intermolecular hydrogen bonds interaction. • UV–visible and the fluorescence emission spectra of the DMB-FBH in aqueous solutions were recorded. • Third order nonlinear optical susceptibility (χ3) of DMB-FBH was determined by Z-scan measurement. Organic nonlinear optical single crystals of (E)-N′-(2,3-dimethoxybenzylidene)-4-fluorobenzohydrazide (DMB-FBH) were synthesized and grown using slow evaporation crystallization from ethanol solution. The single crystal X-ray diffraction scattering revealed that the DMB-FBH crystallised in the tetragonal crystal system with a centro symmetric space group of I 4 1 /a. The crystallographic bond lengths and bond angles were compared with the values generated from optimized molecular geometry based on quantum chemical calculations. The functional group vibrations were identified theoretically by density functional theory with B3LYP 6–311 G (d,p) basis set using Gaussian 09 software package and their vibrations were compared with the experimental FT-IR spectra. The UV-visible and the fluorescence emission spectra of the DMB-FBH in aqueous solutions were recorded. The HOMO-LUMO energy level pictogram addressed the intramolecular charge transfer (ICT) interaction between donor and acceptor moieties and their impact on the energy gap was determined. Different interactions such as O···H, N···H, C···C and C···H in DMB-FBH were quantified via fingerprint plots and these results were compared with that of similar structure. The detailed molecular docking simulation was carried out with M. tuberculosis protein [PDB ID:2 × 22]. The third order nonlinear optical susceptibility (χ3) of DMB-FBH was confirmed experimentally by Z-scan method and their conversion efficiency was higher than the other hydrazones derivatives. In short, this work discusses the crystal structure, identification and quantification of the molecular interactions, thermal, antimycobacterial and optical properties of new hydrazone derivative. Energy frameworks (left) coloumb dispersion (center) and total energy (right) of DMB-FBH crystal structure. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] In the current study, the interaction of SARS-CoV-2 protein (A and B chains of nsp13) with different recently synthesized phenolic compounds (Sreenivasulu et al., Synthetic Communications, 2020, 112–122) has been studied. The interactions have been investigated by using molecular docking, quantum chemical and molecular dynamics simulations methods. The molecular structures of all the ligands are studied quantum chemically in terms of their optimized structures, 3-D orbital distributions, global chemical descriptors, molecular electrostatic potential plots and HOMO-LUMO orbital energies. All the ligands show reasonably good binding affinities with nsp-13 protein. The ligand L2 shows to have better binding affinities to Chain A and Chain B of nsp13 protein, which are −6.7 and −6.4 kcal/mol. The study of intermolecular interactions indicates that L2 shows different hydrophobic and hydrogen bond interactions with both chains. Furthermore, molecular dynamic simulations of the nsp13-L2 complex are obtained over a time scale of 60 ns, which indicates its stability and flexibility behavior as assessed in terms of its RMSD and RMSF graphs. The ADMET analysis also shows no violation of Lipinski rule (RO5) by studied phenolic compounds. We believe that the current findings will be further confirmed by in vitro and in vivo studies of these recent phenolic compounds for their potential as inhibitors for SARS-Co-V-2 virus. [ABSTRACT FROM AUTHOR]