ZnCl2+Urea,the deep eutectic solvent promoted synthesis of the spirooxindolopyrans and xanthenes through a pseudo-three-component approach

Various spirooxindolopyrans and xanthenes were synthesized efficiently through a pseudo-three-component reaction by using deep eutectic solvent (DES) ZnCl₂+Urea. The remarkable advantages of this reaction are the usage of an environmentally benign solvent (DES), simple purification method, operational simplicity, less reaction time, and higher yields making the reaction a green protocol.     

Synthesis,anticancer activity and molecular docking studies of novel pyrido[1,2-a]pyrimidin-4-one derivatives

A series of novel triazolothione, thiadiazole, triazole, and oxadiazole-functionalized pyrido[1,2-a]pyrimidin-4-ones 6a–6l and 7a–7f were prepared, starting from pyridine derivatives 1a and 1b. All the compounds 6a–6l and 7a–7f were screened against four human cancer cell lines (HeLa, COLO205, Hep G2, and MCF 7), among which compounds 6d, 6h, 6j, 7b, and 7e showed promising anticancer activity. Molecular docking studies showed good binding energy and exhibited interactions and better lower free energy values, indicating more thermodynamically favored interaction.     

Synthesis,antibacterial, anticancer and molecular docking studies of macrocyclic metal complexes of dihydrazide and diketone

The complexes of Co(II), Ni(II), Cu(II) and Zn(II) metal ions has been synthesized through template method by the condensation of succinic acid dihydrazide with 5-chloroisatin in alcoholic medium. Complexes were characterized by C H N analysis, molar conductance, thermal analysis, magnetic susceptibility, mass spectrometry, FTIR, EPR, ¹H NMR, UV–Visible spectroscopy. These studies suggest an octahedral geometry for all the complexes. The compounds were found active against B. subtilis and S. aureus and P. aeruginosa and E. coli bacteria. The Zn(II) complex showed significant anticancer activity against Squamous Cell Carcinoma cells tested by the MTT assay method. Molecular docking studies with EGFR tyrosine kinase were also carried out. All these results show that some of the synthesized compounds have remarkable antibacterial and anticancer property.     

One-pot,four-component synthesis of benzylpyrazolyl naphthoquinone derivatives and molecular docking studies

A highly efficient, green, one-pot, four-component approach for the synthesis of benzylpyrazolyl naphthoquinone derivatives (5a–p) have been developed by the domino reaction of 2-hydroxy naphthoquinone, aromatic aldehyde, ethyl acetoacetate, and phenyl hydrazine derivatives in water and employed p-toluene sulfonic acid (p-TSA) as the right choice of catalyst at reflux. Docking simulation was performed to position compounds 5a, 5b, and 5g into the anaplastic lymphoma kinase (ALK) structure active site to determine the probable binding model.     

Synthesis,anticancer, molecular docking and QSAR studies of benzoylhydrazone

To find out effective anticancer compounds we synthesized (1–30) derivatives of 4-isopropylbenzoylhydrazone and evaluated for anticancer potential. The compounds 3, 9, 12, 23, 26 and 28 showed better activities ranging (0.39–1.1 µg/ml) than the standard (1.53 ± 0.01 µg/ml). In line with this, compounds 2, 6, 24, 25 and 29 exhibited better activities compared to the second standard (5FU 4.60 ± 0.01 µg/ml). The best molecular docked complex between the BRCA1 structure and the 1–30 derivatives were analyzed based on the Glide docked score and binding orientation for both the SP and XP mode. The 2D-QSAR analysis reflected a significant correlation between the experimental and the predicted biological activities. The above-mentioned compounds were also assessed by various spectroscopic techniques.     

Kinetic study on the reaction of lauric acid with ethanol catalyzed by deep eutectic solvent based on cetyl trimethyl ammonium bromide

In this work, a novel type of deep eutectic solvents (DES: CTAB–DES) based on cetyl trimethyl ammonium bromide (CTAB) was successfully synthesized by mixing CTAB with p-toluenesulfonic acid monohydrate and applied as catalysts for the esterification reaction of ethanol and lauric acid. The kinetics of the reaction of ethanol and lauric acid catalyzed by CTAB–DES was investigated in the temperature range of 328.15–348.15 K. The influence of different parameters including agitation speed, temperature, catalyst loading, and the lauric acid to ethanol molar ratio on the conversion of lauric acid was discussed. The kinetic experimental data obtained were correlated by the pseudo-homogeneous model, and the results show that it can predict the reaction process well. Moreover, CTAB–DES can be reused six times without any significant decrease in catalytic activity.     

Synthesis,molecular docking studies,and absorption,distribution, metabolism,and excretion prediction of novel sulfonamide derivatives as antibacterial agents

A series of novel sulfonamide‐amide derivatives were synthesized from 3‐(2,4 dichlorophenylamino)‐3‐oxopropane‐1‐sulfonylchloride and a variety of amines under solvent‐free conditions at room temperature. 3‐(2,4‐dichlorophenylamino)‐3‐oxopropane‐1 sulfonylchloride was synthesized in four steps starting from 2,4‐dichloroaniline and chloropropanoic acid in good yield and purity. The synthesized compounds were screened for their in vitro antibacterial activity against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213). Molecular docking of sulfonamide derivatives into S. aureus tyrosyl‐tRNA synthetase (TyrRS)‐active site was also performed and among these, 5m and 5g tightly fit the active sites that might be inhibitors of TyrRS for further investigations. Also in the silico metabolism profile, drug‐like properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) of the title compounds were calculated by the preADMET server.     

Novel imidazole derivatives as antifungal agents: Synthesis,biological evaluation,ADME prediction and molecular docking studies

Abstract

A series of 2-(substituteddithiocarbamoyl)-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide derivatives was designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. All synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and HRMS spectra and elemental analyses. Antifungal activity tests were performed against four different fungal strains. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC₅₀ value 12.5?μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, 5b (2-Pyrrolidinthiocarbonylthio-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide), which can be further optimized as a lead compound.     

Synthesis,bioevaluation and molecular docking study of new piperazine and amide linked dimeric 1,2,3-triazoles

Abstract

In search of more potent new antitubercular agents, a library of novel piperazine tethered dimeric 1,2,3-triazoles were designed by assembling 1,2,3-triazoles and piperazine in a single molecular architectural framework. The titled compounds (3a–m) were synthesized by 1,3-dipolar cycloaddition of 1,4-di(prop-2-yn-1-yl)piperazine (1) and various azides (2a–m) using click chemistry approach with good yields. All the synthesized compounds (3a–m) have been screened for their in vitro antitubercular, antifungal and antioxidant activities against their respective strains. Among them, 3b, 3d, and 3i have revealed promising antitubercular activity against Mycobacterium tuberculosis (Mtb) H37Rv with MIC 12.5?µg/mL. Molecular docking results provided well-clustered solutions to the mode of binding for these molecules into the active site of Mtb enoyl reductase (InhA). In addition to this, most of synthesized compounds were found to have potential antifungal as well as antioxidant activity.     

Bis coumarinyl bis triazolothiadiazinyl ethane derivatives: Synthesis,antiviral activity evaluation,and molecular docking studies

A series of novel 3,3′-(3,3′-(dihydroxy/hydroxyethane-1,2-diyl)bis(7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-6,3-diyl))bis(2H-chromen-2-ones) were prepared by the condensation of thiocarbohydrazide with tartaric acid or malic acid followed by various 3-(2-bromoacetyl)-2H-chromen-2-ones in two steps with good yields. All the synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and mass) data. These synthesized bis(triazolothiadiazinyl coumarin) compounds were evaluated for broad spectrum of antiviral activity. Among all the tested compounds, compound 5f exhibited antiviral activity against H1N1 virus. The molecular docking studies of these compounds against H1N1 neuraminidase enzyme were performed. The binding affinity and binding values were compared with standard drugs.     

Biological contour,molecular docking and antiproliferative studies of DNA targeted histidine based transition metal(II) complexes: Invention and its depiction

A novel series of histidine derived transition metal complexes were synthesized and characterized by multispectral techniques such as UV‐Vis., FT IR, EPR, NMR, ESI‐mass analysis and other physico‐chemical methods like elemental analysis, molar conductivity, magnetic susceptibility. The synthesized compounds were attempted for their biological prospective. The biological studies involved are DNA interaction (binding and damage), antimicrobial, antioxidant, antiproliferative and molecular docking. DNA interaction studies were carried out with the help of UV‐Vis absorption titration, viscosity measurement and cyclic voltammetric techniques which revealed that the synthesized compounds could interact with CT‐DNA through intercalative binding mode. A gel electrophoresis assay demonstrated the ability of complexes to cleave the supercoiled pUC18 DNA. The antioxidant property shows that the metal complexes have preferable ability to scavenge hydroxyl radical than the ligand. Moreover, the antimicrobial assay indicates that these complexes are good antimicrobial agents against various pathogens. Furthermore, the in vitro antiproliferative activities of the complexes were examined on HeLa, Hep G2 and NIH 3 T3 cell lines using an MTT assay. The morphological changes were investigated using Hoechst 33258 staining apoptosis assay. In addition, molecular docking studies were executed to considerate the nature of binding of the synthesized complexes with protein and DNA.     

Heteroscorpionate‐based heteroleptic copper(II) complexes: Antioxidant,molecular docking and in vitro cytotoxicity studies

Three new heteroscorpionate ligands, (2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL¹), (4‐diethylamino‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL²) and (5‐bromo‐2‐hydroxyphenyl)bis(imidazol‐1‐yl)methane (HL³), and their heteroleptic copper(II) complexes of the type [Cu(L^1–3)diimine]ClO₄ ( 1 – 6 ; where diimine =2,2′‐bipyridyl or 1,10‐phenanthroline) have been synthesized and characterized using spectroscopic methods. The molecular structure of ligand HL¹ was determined by single‐crystal X‐ray diffraction. UV–visible, electron paramagnetic resonance and theoretical studies suggest a distorted square pyramidal geometry around copper(II) ion. Analyses of highest occupied and lowest unoccupied molecular orbitals have been used to explain the charge transfer taking place within the complexes. The antioxidant activities of the heteroscorpionate ligands and their heteroleptic copper(II) complexes were determined using ABTS, DPPH and H₂O₂ free radical scavenging assays with respect to standard antioxidant ascorbic acid. In molecular docking studies, the complexes showed π–π, hydrogen bonding, van der Waals and electrostatic interactions with fibroblast growth factor receptor kinase. In vitro cytotoxicity activities of ligands and copper(II) complexes were examined on human breast adenocarcinoma (MCF‐7), cervical (HeLa) and lung (A549) cancer cell lines and normal human dermal fibroblast cell line using MTT assay. Complex 4 exhibited higher anticancer activity than the other complexes against all three cancer lines, being more potent than the standard drug cisplatin.     

Synthesis,antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

In a search for safer and potent antitubercular agents, here a library of newly substituted dioxoisoindolinylmethyl-triazolyl-N-phenylacetamide derivatives (5a–l) has been synthesized via click chemistry approach. All synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB). Among the screened compounds, 5d, 5e, 5h, and 5l showed good antitubercular activity. The compounds 5d and 5l have shown very effective antitubercular activity against Mycobacterium tuberculosis H₃₇Rv (MTB) with MIC 12.5?μg/mL. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral data. We further performed exploratory docking studies on the crystal structure of Mycobacterium tuberculosis enoyl reductase to demonstrate the mechanism of antitubercular activity.     

Diorganotin(IV) carboxylates of 3-methylphenyl ethanoic acid: Synthesis,crystal structure,antibacterial, anticancer and molecular docking studies

Abstract

Di-n-butyl- (1) and diethyltin(IV) (2) derivatives of 3-methylphenylethanoic acid were synthesized and characterized by elemental analysis, atomic absorption, IR, ¹H and 13C NMR spectroscopy and mass spectrometry. The spectroscopic data and single crystal X-ray diffraction studies for complex 2 have confirmed a bidentate coordination mode of the carboxylate ligand and the presence of hexacoordinated tin atoms in the complexes. The complexes were screened for their in vitro antibacterial activity against selected gram positive and gram negative bacterial strains. The anticancer potential was assessed against prostate cancer cell lines. Both complexes have shown higher activities than the ligand acid. Complex 1 with an IC₅₀ value of 4.97?±?0.27?μg/mL was found to be better anti prostate cancer agent than complex 2 (IC₅₀ = 11.26?±?2.18?μg/mL). Molecular docking study has suggested antibacterial action of the complexes in terms of their ability to develop hydrogen bonding and hydrophobic interactions with vital residues of the target proteins like tyrosyl-tRNA synthase from Staphylococcus aureus (gram-positive bacteria) and undecaprenyl diphosphate synthase from Escherichia coli (gram-negative bacteria).     

Design,synthesis, molecular docking,and biological studies of novel phytoestrogen-tanaproget hybrids

A diverse range of novel and highly functionalized flavonoid-based tanaproget hybrids were synthesized and evaluated in vitro for their antimicrobial and antiproliferative activities. Novel products were synthesized in good yields (81–95%) under Pd-catalyzed reaction from bromo flavones and tanaproget boronic acids within 18–20 min at 60 °C. Bioassay results exhibited excellent activities against both hormone-dependent and hormone-independent human breast cancer cells (MCF-7, MDA-MB-231, DU-145, PC-3, and HeLa). Among them, compounds 4e, 9a, 9c, 9e, 9 g, 9 h, 9 m, and 9n displayed excellent activity. Compounds 4d, 4o, and 9o were found equally potent against C. albicans compared to fluconazole. Compound 5c showed better antibacterial activity against S. aureus. Compounds 5a, 9i, 9o, and 10c have shown admirable antibacterial activity against E. coli.     

Synthesis,crystal structures and spectral characterization of Cu(II) and Mn(II) complexes of 4-hydroxy-3-methoxybenzaldehyde: antioxidant properties and molecular docking studies

[Cu(L)₂(H₂O)₂] (1) and [Mn(L)₂(H₂O)₂] (2) (HL = 4-hydroxy-3-methoxybenzaldehyde) were synthesized and characterized using elemental, spectral (FTIR, ESI-MS, UV–visible, fluorescence and EPR), thermal, cyclic voltammetric, powder, and single crystal X-ray crystallographic studies. Spectral and X-ray data ascertained the structural features, binding modes of ligand and distorted octahedral geometry around the metal ions. Cyclic voltammetric studies confirmed the formation of a quasi reversible redox couple in solution. Crystal structure analysis of 1 and 2 reveal the presence of non-covalent interactions, resulting in a 1-D polymeric chain. Antioxidant properties (using DPPH and hydrogen peroxide assay) and molecular docking studies (using 1BNA) are also examined. The binding free energies (calculated from docked models), ?270 (1) and ?295 kJ mol^?1 (2), suggest that the complexes reasonably bind to DNA, and the DNA-binding affinity of 2 is stronger than that of 1.     

Synthesis,anticancer and antimicrobial evaluation of new pyridyl and thiazolyl clubbed hydrazone scaffolds

Abstract

A series of new hydrazones bearing pyridyl and thiazolyl scaffolds have been synthesized and evaluated for their in vitro anticancer and antimicrobial activities. The anticancer activity was evaluated against the A549 lung cancer cell line. The eight hydrazone derivatives have shown better anticancer activity than positive control doxorubicin against the A549 lung cancer cell line. The antimicrobial activity was evaluated against bacterial and fungal pathogens by using well diffusion method. The four hydrazone derivatives have displayed good antimicrobial activities. Molecular docking studies of the synthesized hydrazone derivatives revealed good binding via hydrogen bond interactions with key residues on active sites as well as neighboring residues with an active site of Focal adhesion kinase (PDB ID 2JKO). A computational study for the prediction of absorption, distribution, metabolism, and excretion (ADME) properties of all compounds has also been performed.     

Choline chloride based eutectic solvent for the efficient synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives via multicomponent reaction under mild conditions

Synthesis of 2-amino-4H-chromen-4-ylphosphonate derivatives has been accomplished by the one-pot three-component reaction of salicylaldehyde, malononitrile/ethylcyanoacetate and dialkyl phosphites in the presence of reusable deep eutectic solvent (DES) under mild conditions. The advantages of this method are mild reaction conditions, simple work-up procedure, use of DES as a green solvent and an economical protocol for the preparation of important biologically active phosphorus-containing compounds.     

2-methylindole analogs as cholinesterases and glutathione S-transferase inhibitors: Synthesis,biological evaluation,molecular docking,and pharmacokinetic studies

In this study, we aimed to (i) synthesize new 2-methylindole analogs containing various amino structures, pyrrolidine, piperidine, morpholine, and substituted phenyl groups through structural and molecular modifications, (ii) evaluate the pharmaceutical potential of 2-methylindole analogs via assessing enzyme inhibitory activity against glutathione S-transferase (GST), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), (iii) predict ADMET and pharmacokinetic properties of the synthesized 2-methylindole analogs, (iv) reveal the possible interactions between the synthesized 2-methylindole analogs with GST, AChE, and BChE enzymes using several molecular docking software. In vitro enzyme inhibition assays showed that the synthesized indole analogs exhibited moderate to good inhibitory activities against GST, AChE, and BChE enzymes. Briefly, the inhibitory activities of the analogs 4b and 4i against AChE, 4a and 4b against BChE, and analogs 1 and 4i against GST were detected to be higher or close to the standard inhibitor compounds. The analog 4b was detected to have the best inhibitory activity against both AChE and BChE enzymes with the lowest IC₅₀ values as 0.648 µM for AChE and 0.745 µM for BChE. The analyses of enzyme inhibition relationship with the synthesized analogs could help to design new analogs for the inhibitors of cholinergic and glutathione pathways based on the indole derivatives.