Design, Spectroscopic, and Crystal Structural Characterization of New Pyrazolone-Based Schiff Bases: Molecular Docking Investigations against SARS-Covid-19 Main Proteases (PDB Ids: 6LU7 and 7TLL)

New pyrazolone-based Schiff bases were synthesized and characterized by various spectroscopic and analytical techniques such as 1H-NMR, FTIR, and UV − Vis spectroscopy and elemental analysis. Crystal structures of two of the Schiff-base (SB) compounds were obtained by single-crystal X-ray crystallography (SCXRC). The target Schiff bases were synthesized from the condensation of 4-acetyl-3-methyl-1-phenyl-5-pyrazolone with 1,2-diaminobenzene (SB1), 4-methyl-1,2-diaminobenzene (SB2), and 4,5-dimethy-1,2-diaminobenzene (SB3). Molecular docking modeling was used to study the interactions of these molecules with SARS-CoV-2 virus main proteases (PDB ids: 6LU7 and 7TLL). The estimated free binding energies (EFBE) for all the three SBs were better than the standard drugs favipiravir and dexamethasone. Besides, the order of EFBE was −7.68 (SB3)> −7.36 (SB1)> −7.06 kcal.mol−1(SB2) for 6LU7 and −10.42 (SB3)> −10.05 (SB1)> −9.69 kcal.mol−1(SB2) for 7TLL. SB3 showed the best interactions with both proteases that is discussed based on structure–function relationship.

Novel oxazolidinone zinc(II) complexes as antibacterial and anti-SARS-CoV-2 agents: synthesis, characterization, DFT calculations, ADMET, in silico molecular docking and biological activities

A series of Zn(II) complexes with oxazolidinone derivatives has been synthesized and characterized using spectroscopic techniques: IR, H-1 NMR, UV-Vis spectroscopy, and TGA/DTG thermal investigation. Theoretical computations were carried out using B3LYP/6-31G(d) and B3LYP/LanL2DZ to analyze the vibrational properties, NBO charges, global chemical reactivity indices and to illustrate the FOMs. TD-DFT calculations using WB97XD functional were realized with 6-31 G(d) and LAN2DZ basis set on oxazolidinone ligands and their zinc complexes. The pharmacokinetic properties and toxicity of the investigated compounds were predicted using in silico ADMET studies. Moreover, the S. aureus, E. coli, S. pneumoniae, ribosome 50S subunit, SARS-Cov-2 spike protein and ACE2 human receptor were selected for molecular docking study. The docking study shows that HL4 and ZnL4 bind better to the spike protein and hACE2 receptor. The redox properties were also studied for ligands and their corresponding complexes using cyclic voltammetry. Finally, antioxidant activity studies using DPPH radical scavenging showed efficiency for HL2 and [Zn(L-2)(2)] with low values of IC50 compared to ascorbic acid. The antimicrobial activity against B. subtilis (ATCC 9372), E. faecalis (ATCC 29212), S. aureus (ATCC 6538), E. coli (ATCC 4157), bacteria strains, C. albicans (ATCC 24433) and A. niger fungi strains were evaluated.

Promising Schiff bases in antiviral drug design and discovery.

Emerging and re-emerging illnesses will probably present a new hazard of infectious diseases and have fostered the urge to research new antiviral agents. Most of the antiviral agents are analogs of nucleosides and only a few are non-nucleoside antiviral agents. There is quite a less percentage of marketed/clinically approved non-nucleoside antiviral medications. Schiff bases are organic compounds that possess a well-demonstrated profile against cancer, viruses, fungus, and bacteria, as well as in the management of diabetes, chemotherapy-resistant cases, and malarial infections. Schiff bases resemble aldehydes or ketones with an imine/azomethine group instead of a carbonyl ring. Schiff bases have a broad application profile not only in therapeutics/medicine but also in industrial applications. Researchers have synthesized and screened various Schiff base analogs for their antiviral potential. Some of the important heterocyclic compounds like istatin, thiosemicarbazide, quinazoline, quinoyl acetohydrazide, etc. have been used to derive novel Schiff base analogs. Keeping in view the outbreak of viral pandemics and epidemics, this manuscript compiles a review of Schiff base analogs concerning their antiviral properties and structural-activity relationship analysis.

A pyrazolone-based dinuclear Cu(II) Schiff-base complex: DFT studies on the rate-determining steps of the tautomerism in the ligand and molecular docking modelling with COVID-19 main protease (6LU7)

A new dinuclear Schiff-base complex, [Cu2L'2(μ-OAc)2], was synthesized and characterized by various spectroscopic methods and single-crystal X-ray diffraction (SCXRD). The symmetrical H2L ligand was synthesized from the reaction between 4-acetyl-3-methyl-1-phenyl-2-pyrazoline-5-one (or acylpyrazolone) with 1,3-propanediamine, but upon reaction with a metal salt, it gave the unsymmetrical HL'. The transition states and rates of interconversion between different tautomeric forms of HL' were studied by DFT computations. The imine-one (Z) in the gas phase and imine-ol (Z) in the solution were the most stable forms, most probably due to better hydrogen bonding. We also applied molecular docking modeling on the various tautomeric forms of the ligand as well as the complex with the main protease (6LU7) of the SARS-CoV-2 virus. Based on the obtained results, the complex had better interactions with the receptor. The order of the interactions was [Cu2L2(μ-OAc)2] > amine-one (Z) > imine-one (E) > imine-ol (Z) > amine-one (E) > imine-one (Z) > imine-ol (E). [ FROM AUTHOR] Copyright of Journal of Coordination Chemistry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Synthesis and in Silico Investigation of Organoselenium-Clubbed Schiff Bases as Potential Mpro Inhibitors for the SARS-CoV-2 Replication.

Since the first report of the organoselenium compound, ebselen, as a potent inhibitor of the SARS-CoV-2 Mpro main protease by Z. Jin et al. (Nature, 2020), different OSe analogs have been developed and evaluated for their anti-COVID-19 activities. Herein, organoselenium-clubbed Schiff bases were synthesized in good yields (up to 87%) and characterized using different spectroscopic techniques. Their geometries were studied by DFT using the B3LYP/6-311 (d, p) approach. Ten FDA-approved drugs targeting COVID-19 were used as model pharmacophores to interpret the binding requirements of COVID-19 inhibitors. The antiviral efficiency of the novel organoselenium compounds was assessed by molecular docking against the 6LU7 protein to investigate their possible interactions. Our results showed that the COVID-19 primary protease bound to organoselenium ligands with high binding energy scores ranging from -8.19 to -7.33 Kcal/mol for 4c and 4a to -6.10 to -6.20 Kcal/mol for 6b and 6a. Furthermore, the docking data showed that 4c and 4a are good Mpro inhibitors. Moreover, the drug-likeness studies, including Lipinski's rule and ADMET properties, were also assessed. Interestingly, the organoselenium candidates manifested solid pharmacokinetic qualities in the ADMET studies. Overall, the results demonstrated that the organoselenium-based Schiff bases might serve as possible drugs for the COVID-19 epidemic.

Design, synthesis, and computational studies of novel imidazo[1,2-a]pyrimidine derivatives as potential dual inhibitors of hACE2 and spike protein for blocking SARS-CoV-2 cell entry.

In the present work, a new series of imidazo[1,2-a]pyrimidine Schiff base derivatives have been obtained using an easy and conventional synthetic route. The synthesized compounds were spectroscopically characterized using 1H, 13C NMR, LC-MS(ESI), and FT-IR techniques. Green metric calculations indicate adherence to several green chemistry principles. The energy of Frontier Molecular Orbitals (FMO), Molecular Electrostatic Potential (MEP), Quantum Theory of Atoms in Molecules (QTAIM), and Reduced Density Gradient (RDG) were determined by the Density Functional Theory (DFT) method at B3LYP/6-31 G (d, p) as the basis set. Moreover, molecular docking studies targeting the human ACE2 and the spike, key entrance proteins of the severe acute respiratory syndrome coronavirus-2 were carried out along with hACE2 natural ligand Angiotensin II, the MLN-4760 inhibitor as well as the Cannabidiolic Acid CBDA which has been demonstrated to bind to the spike protein and block cell entry. The molecular modeling results showed auspicious results in terms of binding affinity as the top-scoring compound exhibited a remarkable affinity (-9.1 and -7.3 kcal/mol) to the ACE2 and spike protein respectively compared to CBDA (-5.7 kcal/mol), the MLN-4760 inhibitor (-7.3 kcal/mol), and angiotensin II (-9.2 kcal/mol). These findings suggest that the synthesized compounds may potentially act as effective entrance inhibitors, preventing the SARS-CoV-2 infection of human cells. Furthermore, in silico, ADMET, and drug-likeness prediction expressed promising drug-like characteristics.

Virtual and in vitro, in vivo Screening of Transition Metal Complexes of N,N-Chelating Ligand: Experimental and Theoretical Investigations

Several transition metal complexes [ML(phth)], where M = Cu(II), Zn(II), Co(II) and Ni(II), X = phthalic acid and L = Schiff base generated from benzene-1,2,diamine and 4-chlorobenzaldehyde, were synthesized and characterized by IR, UV-Vis, 1H NMR, 13C NMR and mass spectra. According to the physico-chemical studies, all the synthesized metal(II) complexes have a square planar geometry. The DNA nuclease activity of the synthesized metal complexes was investigated using UV absorption assay and viscosity, validating the intercalative mechanism of binding. Antimicrobial activity of the ligand and its metal(II) complexes on various microorganisms was also investigated. The optimal form and biological accessibility of the metal complexes were examined by the Gaussian 09W algorithm. These compounds were screened for drug-like activity and pharmacokinetic studies using the free SWISS ADME online software. The positive outcomes of molecular docking studies on the COVID-19 virus and cancer DNA are interesting. © 2023 Chemical Publishing Co.. All rights reserved.

Chitosan Schiff base electrospun fabrication and molecular docking assessment for nonleaching antibacterial nanocomposite production.

In this work, new chitosan derivative nanofibers that exhibit antibacterial properties were successfully fabricated. The two CS Schiff base derivatives (CS-APC and CS-2APC) were prepared by incorporating 4-amino antipyrine moiety in two different ratios, followed by a reductive amination to obtain the corresponding derivatives CS-APCR and CS-2APCR. Spectral analyses were used to confirm the chemical structure. The molecular docking evaluation of CS-APC, CS-APCR, and CS was conducted on DNA topoisomerase IV, thymidylate kinase and SARS-CoV-2 main protease (3CLpro) active sites. CS-APCR showed a well-fitting into the three enzyme active sites with docking score values of - 32.76, - 35.43 and - 30.12 kcal/mol, respectively. The nanocomposites of CS derivatives were obtained by electrospinning the blends of CS-2APC and CS-2APCR with polyvinyl pyrrolidone (PVP) at 20 kV. The morphology of the nanofibers was investigated by scanning electron microscopy (SEM). It was found that fiber diameters were significantly decreased when CS-2APC and CS-2APCR were incorporated into pure PVP to reach 206-296 nm and 146-170 nm, respectively, compared to 224-332 nm for pure PVP. The derivatives of CS and their nanofibers with PVP were found to have antibacterial activities against two strains of Staphylococcus aureus and Escherichia coli. Data revealed that CS-2APC nanofibers showed antibacterial activity to the two strains of E. coli less than CS-2APCR nanofibers.

Structural and theoretical investigations, Hirshfeld surface analysis and anti-SARS CoV-2 of nickel (II) coordination complex.

A nickel(II) Schiff base complex, [Ni(L)(DMF)](1), was synthesized by treating NiCl2.6H2O with an ONS-donor Schiff base ligand(H2L) derived from the condensation 3,5-Dichlorosalicylaldehyde and 4,4-Dimethyl-3-thiosemicarbazide in DMF. The geometry around the center metal ion in [Ni(L)(DMF)](1) was square planar as revealed by the data collection from diffraction studies. DFT calculations were performed on the complex to get a structure-property relationship. Hirshfeld surface analysis was also carried out in the crystal structure of nickel (II) Schiff base complex. Additionally, inspiring from recent developments to find a potential inhibitor for SARS-CoV-2 virus, we have also performed molecular docking study of [Ni(L)(DMF)](1) to see if our novel complex show affinity for main protease (Mpro) of SARS-CoV-2 Mpro (PDB ID: 6LZE). Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant was found to be -6.6 kcal/mol and 2.358 µM, respectively, for the best docked confirmation of complex [Ni(L)(DMF)](1) with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of complex [Ni(L)(DMF)](1) is found to be better than that of recently docking results of anti-SARS-CoV-2 drugs like chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) when targeted to the active-site of SARS-CoV-2 Mpro. Besides this, molecular docking against G25K GTP-nucleotide binding protein (PDB ID: 1A4R) was also studied. We believe that current results can intrigue not only for the biomedical community but also for the materials chemists who are engaged to explore the application coordination complexes.Communicated by Ramaswamy H. Sarma.

Copper(II) Chelates of Schiff Bases Enriched with Aliphatic Fragments: Synthesis, Crystal Structure, In Silico Studies of ADMET Properties and a Potency against a Series of SARS-CoV-2 Proteins.

We report two complexes [Cu(LI)2] (1) and [Cu(LII)2] (2) (HLI = N-cyclohexyl-3-methoxysalicylideneimine, HLII = N-cyclohexyl-3-ethoxysalicylideneimine). The ligands in both complexes are trans-1,5-N,O-coordinated, yielding a square planar CuN2O2 coordination core. The molecule of 1 is planar with two cyclohexyl groups oriented to the opposite sites of the planar part of a molecule, while the molecule of 2 is significantly bent with two cyclohexyl groups oriented to the same convex site of a molecule. It was established that both complexes in MeOH absorb in the UV region due to intraligand transitions and LMCT. Furthermore, the UV-vis spectra of both complexes revealed two low intense shoulders in the visible region at about 460 and 520 nm, which were attributed to d-d transitions. Both complexes were predicted to belong to a fourth class of toxicity with the negative BBB property and positive gastrointestinal absorption property. According to the molecular docking analysis results, both complexes are active against all the applied SARS-CoV-2 proteins with the best binding affinity with Nsp 14 (N7-MTase), PLpro and Mpro. The obtained docking scores of complexes are either comparable to or even higher than those of the initial ligands. Complex 1 was found to be more efficient upon interaction with the applied proteins in comparison to complex 2. Ligand efficiency scores for the initial ligands, 1 and 2 were also revealed.

Metal complexes of Tridentate Schiff base: Synthesis, Characterization, Biological Activity and Molecular Docking Studies with COVID-19 Protein Receptor.

Mononuclear chelates of Cr(III), Mn(II), Fe(III), Ni(II), Cu(II), Zn(II) and Cd(II) resulted from new tridentate Schiff base ligand, 4-((1-(5-acetyl-2,4-dihydroxyphenyl)ethylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, were synthesized. Metal to ligand ratio was found to be1 : 1, which was revealed via elemental analysis and characterized via various spectroscopic tools. IR has point out that the coordination of the ligand towards the metal ions was carried out via NOO donor atoms. UV-Vis, 1H NMR spectral data, molar conductivity measurements, BET surface area, melting points and theoretically through density function theory were used such as characterizing techniques in supporting further interpretation of the complexes structures. The complexes were octahedral except Cu(II) and Ni(II) complexes were tetrahedral as suggested from the magnetic moment measurement. The complexes were found to have surface area, pore volume and particle radius of 23-176 m2 g-1, 0.02-0.33 cc/g and 8.71-4.32 nm, respectively, as pointed out from BET measurement. Schiff base ligand and metal complexes were tested in vitro to estimate their antimicrobial activity opposed to Gram-negative and Gram-positive bacterial and fungal organisms. MOE 2008 was used headed for screen potential drugs with molecular docking by the protein sites of new coronavirus and the study was constructed to molecular docking without validation through MD simulations.

DFT calculations, molecular docking, in vitro antimicrobial and antidiabetic studies of green synthesized Schiff bases: as Covid-19 inhibitor.

In this investigation, we synthesized Schiff bases 2-(2-methoxyphenoxy)-N-(4-methylbenzylidene)ethanamine, N-(4-methoxybenzylidene)-2-(2-methoxyphenoxy)ethanamine and 2-(2-methoxyphenoxy)-N-(4-nitrobenzylidene)ethanamine from 2-(2-methoxyphenoxy)ethanamine and various aromatic aldehydes by the environmentally friendly sonication method. The B3LYP method with a 6-311++G (d, p) basis set was used in the DFT calculation to obtain the optimized structure of the Schiff base MPEA-NIT. The compounds were tested in vitro for inhibition of bacterial growth (disc well method) and inhibition of α-amylase (starch-iodine method). The compounds tested showed inhibitory activities. In addition, they were subjected to PASS analysis, drug likeness, and bioactivity score predictions using online software. To confirm the experimental findings, molecular docking analyses of synthesized compounds on α-amylase (PDB ID: 1SMD), tRNA threonylcarbamoyladenosine (PDB ID: 5MVR), glycosyl transferase (PDB ID: 6D9T), and peptididoglycan D,D-transpeptidase (PDB ID: 6HZQ) were performed. The emergence of a new coronavirus epidemic necessitates the development of antiviral medications (SARS-CoV-2). Docking active site interactions were investigated to predict compounds' activity against COVID-19 by binding with the SARS-CoV-2 (PDB ID: 6Y84).Communicated by Ramaswamy H. Sarma.

New Schiff base copper(II) and nickel(II) complexes for biomedical applications with reference to SARS-CoV-2 and HIV virus

A series of nickel(II) and copper(II) complexes viz. [Ni(L1)2](1), [Cu(L1)2](2), [Ni(L2)2](3) and [Cu(L2)2](4) (where L1H=(E)-N-phenyl-2-(thiophen-2-ylmethylene)hydrazine-1-carboxamide, L2H=(E)-2-((3-methylthiophen-2-yl) methylene)N-phenylhydrazine-1-carbothioamide), have been synthesized and designed as potential inhibitors against SARS-CoV-2 and HIV-1 virus. The quantum computational calculations are used for structure-property relationship. A detailed structural and non-covalent supramolecular interaction in the ligand (L1H) is investigated by single crystal structure analysis and computational approaches. Hirshfeld surface analysis is done in the crystal structure of the ligand (L1H), while 3D topology of the crystal packing is visualized through an energy framework. To find potential inhibitors of the SARS-CoV-2 and HIV-1 virus, molecular docking of the ligands and their corresponding metal complexes with SARS-CoV-2 and HIV-1 virus is performed. The X-ray crystallographic structure of the main protease of the SARS-CoV-2 (PDB ID: 7VNB) and HIV-1 virus (PDB ID: 1REV) is retrieved from the protein data bank and used as receptor proteins. The molecular docking results has shown that Schiff bases and their complexes with SARS-CoV-2 and HIV-1 virus exhibited good binding affinity at binding site of receptor protein. It is also observed that the binding affinities of the Schiff bases and metal complexes towards SARS-CoV-2 are comparatively higher than the HIV virus. This study may offer the new antivirus drug candidates against SARS-CoV-2 and HIV-1 virus. © 2022 Indian Journal of Chemistry (IJC). All right reserved.

A Schiff Base with Polymorphic Structure (Z′ = 2): Investigations with Computational Techniques and in Silico Predictions

In this study, we report a newly synthesized Schiff base molecule named (E)-N-(2-chloropyridin-3-yl)-1-(5-nitro-2-(piperidin-1-yl)phenyl)methanimine. We also report its structural, chemical, surface, and electronic properties, potential targets, drug-likeness, ADME and toxicity profile, and docking studies for the main protease (Mpro) of SARS-CoV-2. The scope of this study includes the topological and electronic properties, intermolecular interactions, physicochemical and pharmacokinetic properties, metabolic pathways, toxicity endpoints, blood–brain barrier (BBB) permeability, and intestinal absorption activities. We performed the above analyses using bioinformatics/chemoinformatics tools and computational techniques. The topic crystal/compound (TC) contains two crystallographically independent molecules in the asymmetric unit (Z′ = 2). TC is open to attack by electrophilic and nucleophilic species and is a soft, chemically reactive, kinetically unstable material. There are no deviations from the known drug-likeness rules. BBB penetration and GI absorption of TC are possible. The docking values of the complex Mpro/TC and Mpro/native ligand N3 were calculated to be −8.10 and −7.11 kcal/mol, respectively. Therefore, we can say that TC is a potential Mpro inhibitor and can be investigated for further laboratory studies. © 2023 Taylor & Francis Group, LLC.

Influence of hydroxyl group in stabilizing the Schiff base crystal structure: Crystal structure, computational and molecular docking studies

To investigate the synergetic effect in the formation of crystal structure having two independent molecules in the asymmetric unit and the structure-property relationship of the molecule, we have synthesized the Schiff base compound (E)-4-(((4-chlorobenzyl)imino)methyl)benzene-1,2,3-triol. The formation of the desired compound was confirmed by the FTIR and single-crystal X-ray studies. The enriched hydroxyl group exhibits more intra and inter-strong hydrogen bonds. The chlorine-hydrogen and C6-H6‧‧‧π interaction along with other interactions form a supramolecular architecture. The Hirshfeld surface analysis and 2D fingerprint analysis provide valuable information about the intermolecular interaction present in the crystal structure. The likelihood of occurrence of intermolecular contacts present in the crystal structure was analyzed using enrichment ratio. The visualization of the interaction topology along with interaction energy between the molecules are carried out using an energy framework. QTAIM, NCI, ELF and LOL studies provide information about electron charge density distribution and the nature of intramolecular and dimeric interaction. The DFT studies provide ground state energy of the optimized structure and the HOMO-LUMO energy gap. The molecular electrostatic potential provides the reactive site and anisotropy of charge distribution of chlorine atom. The NBO studies provide stabilization energy associated with the delocalization of orbitals. The docking studies were also carried out for SARS COVID-19 and the effect of hydroxyl group substitution on binding interaction was investigated.

Synthesis, structural investigations, XRD, DFT, anticancer and molecular docking study of a series of thiazole based Schiff base metal complexes

A novel Schiff base (SB) ligand, abbreviated as HDMPM, resulted from the condensation of 2-amino-4 -phenyl-5-methyl thiazole and 4-(diethylamino)salicyaldehyde, and its metal complexes with [Co(II), Cu(II), Ni(II), and Zn(II)] ions in high yield were formed. The physico-chemical techniques such as elemental analysis, molar conductance, IR, 1 H and 13 C NMR, mass spectroscopy, and electronic absorption studies were utilized to characterize the synthesized compounds. The studied compounds were examined for their possible anticancer activity against a number of human cancerous cell lines, including A549 lung carcinoma, HepG2 liver cancer, HCT116 colorectal cancer, and MCF-7 breast cancer cell lines, with dox-orubicin serving as the standard. The study revealed that Zn(II) complex showed significant activity to inhibit growth of HepG2, MCF7, A549, and HCT116 cell lines by a factor of 88, 70, 75, and 70, respec-tively, when compared to untreated. In addition, the reported compounds were optimized by employing Gaussian16 program package with B3LYP functional incorporating dispersion with two different basis sets (LanL2DZ and 6-31G(d,p)). Moreover, Autodock Vina software was used to assess the biological effective-ness of the studied compounds against SARS-CoV-2 Omicron variant (PDB ID: 7T9K).(c) 2022 Elsevier B.V. All rights reserved.

Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff base ligands: synthesis, characterization, DFT, in vitro antimicrobial activity and molecular docking studies

Three Schiff base ligands [H2L1-H2L3] containing nitrogen/oxygen donor atoms and their Co(II), Ni(II), Cu(II) and Zn(II) complexes were synthesized by stirring metal acetates with Schiff base ligands obtained from condensation reaction of 2-amino-6-chloro-4-nitrophenol with 5-chloro salicylaldehyde/3,5-dibromo salicylaldehyde/3-methoxy-5-nitro salicylaldehyde. The structural traits of the synthesized compounds were done by using elemental analysis, spectroscopic techniques (UV-Vis, H-1 and C-13 NMR, FT-IR), mass spectrometry and some physical studies (XRD, TGA). According to spectral data, ligands behave as a tridentate (ONO) and formed complexes with octahedral geometry. The thermogravimetric analysis revealed that metal complexes decay in multi-steps leaving metal oxide as an end product. Powder XRD study suggested crystalline nature of the compounds. The energy gap (HOMO-LUMO) and molecular electrostatic potential calculation were computed by using DFT/B3LYP/6-31G** basis set. Derived ligands and complexes were explored for in vitro antimicrobial potential toward two gram-positive bacteria, two gram-negative bacteria, i.e., S. aureus, B. subtilis, P. aeruginosa, E. coli, and two fungal strains, i.e., A. niger, C. albicans, through serial dilution method taking ciprofloxacin and fluconazole as standard. The investigated results showed that complexes are more potent than free Schiff base ligands. The Cu(L-2)(H2O)(3) (0.0115 mu mol/mL) and Zn(L-2)(H2O)(3) (0.0115 mu mol/mL) complexes were found to be more active among all the investigated compounds. Additionally, molecular docking studies were also performed for some compounds in the active site of DNA Gyrase enzyme (PDB code: 1AJ6), suggesting good hydrophobic interactions of compounds with the enzyme.

Synthesis, characterization, computational analyses, in silico ADMET studies, and inhibitory action against SARS-CoV-2 main protease (Mpro) of a Schiff base

COVID-19 disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has struck the whole world and raised severe health, economic, and social problems. Many scientists struggled to find a vaccine or an antiviral drug. Eventually, both vaccines and recommended drugs, repurposed drugs, or drug combinations were found, but new strains of SARS-CoV-2 continue to threaten human life and health. As part of the fight against COVID-19 disease, this study involves an in silico molecular docking analysis on the main protease (Mpro) of SARS-CoV-2. To this aim, a Schiff base compound was synthesized and characterized using spectroscopic techniques, including X-ray, FTIR, and UV-Vis. Surface analysis and electronic properties of this molecule were investigated using the DFT method. The drug-likeness parameters of the title compound were studied according to the rules of Lipinski, Veber, Ghose, Egan, and Muegge and were found in agreement with these rules. In silico toxicity analyses revealed that the new compound is a potentially mutagenic and carcinogenic chemical. The title compound was predicted to be an inhibitor of cytochrome P450 enzymes (5 CYPs). This inhibitory effect indicates a weak metabolism of the molecule in the liver. In addition, this compound was displayed good intestinal absorption and blood-brain barrier penetration. The druggability properties of the title compound were investigated, and Swiss Target Prediction predicted it to be a protease inhibitor. In this context, the SARS-CoV-2 main protease was selected as a biological target in molecular docking studies. Docking results were compared with the known native ligand N3 inhibitor. The value of binding energy between the Schiff base compound and the binding pocket of the main protease is higher than that of the reference ligand N3. The calculated free energies of binding of the Schiff base compound and the reference ligand N3 are -8.10 and -7.11 kcal/mol, respectively.

The dual therapeutic effect of metformin nuclei-based drugs modified with one of Tulbaghia violacea extract compounds

Novel Schiff base was synthesized from the condensation reaction of metformin with [4-(Diethylamino) benzaldehyde (NBM). Different metal complexes were prepared using Pd (II), Pt (II), Cu (II), and V (IV) metal ions. All complexes showed the nonelectrolytic behavior. So, the expected molecular formulas for complexes were [Pd (NBM)Cl2], [Pt (NBM)Cl2], [Cu (NBM)2Cl2] and [VO (NBM)2]. The cytotoxicity of (NBM) Schiff base and its metal complexes on human cancer cell line, MCF-7, was investigated. V (IV) and Cu (II) complexes showed potential blood glucose lowering effect higher than the commercial metformin drug. VO (II) complex has superior antioxidant activity more than the other synthesized compounds and the standard ascorbic acid. Molecular docking investigation proved the presence of interesting interactions between all synthesized compounds with the active site amino acids of EGFR tyrosine kinase (anticancer activity). The molecular docking of metal complexes has observed effective inhibition for the specific mTOR protein that is expected to aid the growth of the COVID-19 virus. © 2022 John Wiley & Sons, Ltd.

Structural-property relationship in halogen-bonded Schiff base derivative: Crystal structure, computational and SARS-CoV-2 docking

We synthesized the halogenated Schiff base compound to understand the influence of halogen and hydrogen bonding interactions. The Schiff base compound is characterized by FTIR, SEM-EDAX and single-crystal X-ray diffraction studies. The structural studies reveal that the 4-chloro-2-(((4-chlorobenzyl) imino) methyl) phenol crystallizes in the monoclinic, P 2 1 / n space group. The O1-H1 center dot center dot center dot N1 strong hydrogen bond forms the intramolecular pseudo chelating ring motif and acts as a coordinating site for metal complexes. The intra, intermolecular and 7r center dot center dot center dot 7r interactions were involved in the construction of supramolecular architecture. The interesting type-I halogen bonds having trans geometry are exhibited. Hirshfeld surface analysis supports the interactions observed in the crystal structure, and the energy framework analysis provides the stabilization interaction energy among the molecular pairs. The enrichment ratio provides favored contacts between the atomic pair and gives strong validation to the halogen center dot center dot center dot halogen and halogen center dot center dot center dot hydrogen bonds. The DFT studies give more insight into electronic structure and provide a global and local parameter of the molecule. NBO studies provide stabilization energy and charge transfer within the molecule. The QTAIM studies were used to calculate the strength of the halogen, hydrogen and stacking intermolecular interaction. Further, docking studies were carried out for COVID-19 proteins to reveal the structural-function properties of halogen and hydrogen bonds present in the synthesized compound.