Synthesis, characterization, in vitro anticancer activity, and docking of Schiff bases of 4-amino-1,2-naphthoquinone (original) (raw)
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Journal of Taibah University for Science
In this study, versatile multifunctional Schiff base (SB) derivatives were synthesized. Compounds 1-8 were prepared by a mild condition and were pharmacologically assessed for their role in vitro anti-cancer and their impact on human fibrosarcoma (HT-1080) and cervical cancer cells (HeLa), in addition to their antimicrobial activity regarding fungal strains, gram-positive and gramnegative bacteria. Preliminary in silico study of 1-8 and the standard compound (5-Fluorouracil) was accomplished, using Drug2Way and PASS software. Besides, docking investigations were carried out using Schrödinger software to determine the interaction of p53-MDM2 and pf-DHFR binding affinity for all the compounds. The antimicrobial results exhibited that these novel compounds have modest to good inhibitory action against the tried bacterial and fungal strains. The crystal structures of 2 and 7 have been determined. Hirshfeld Surface Analysis (HSA) is in agreement with the XRD studies. Both compounds have shown enol-imine tautomeric forms as EE isomer.
Structural and molecular docking studies of biologically active mercaptopyrimidine Schiff bases
Journal of Molecular Structure, 2017
Novel Schiff bases derived from the treatment of mercapto-diamino pyrimidine with two different aldehydes are characterized using elemental analysis, single crystal X-ray diffraction and 1 H-NMR spectroscopy. The pharmacological action of the synthesized compounds viz., antimicrobial, anticancer and antitubercular activities is studied. The Schiff bases show a very good activity against various test pathogens. DNA and β-CD binding interactions of the compounds are studied using UV-Visible absorption and fluorescence spectral measurements. The binding constants of the compounds towards β-CD are in the order of 10 3 to 10 4. Molecular docking is done using MOE program on the 3D structure of the enzymes, viz., human thymidylate synthase complexed with dump and raltitrex, candida albicans N-myristoyltransferasepeptidic inhibitor, catalytic domain of protein kinase pKnb from mycobacterium tuberculosis in complex with mitoxantrone, pare, topoisomerase atpase inhibitor, E. coli and lactobacillus casdihydrofolatereductase. The MIC/IC 50 values of the Schiff bases are compared with the glide scores from the molecular docking studies. The number of hydrogen bonding interactions between the Schiff bases and amino acid residues are also reported.
Journal of Adhesion Science and Technology, 2020
Two Schiff bases derived from aminobenzothiazole derivatives with Salicylaldehyde/Bromosalicylaldehyde namely 2-[6-Methylbenzothiazol-2-ylimino) methyl phenol (1) and 3-Bromo-2-[6-methylbenzothiazol-2-ylimino) methyl phenol (2) were synthesized using simple condensation method and characterized using various spectral techniques like FT-IR, NMR, analytical data and single crystal XRD. Schiff base 1 crystallized in monoclinic crystal system with the space group P121/n1. Schiff base 2, the structure was optimized using Gaussian 09 program (UB3LYP methods, [6-31G (d, p)] basis sets). The antimicrobial activity of the Schiff bases was screened for various test organisms like Pseudomonas aeruginosa (P. aeroginosa) (ATCC: 15442), Escherichia coli (E. coli) (ATCC: 5922), Serratia marcescens (S. marcescens) (ATCC: 14756), Acinetobacter baumannii (A. baumauii) (ATCC: 43498), Aspergillus niger (A. niger) (ATCC: 6275) and Candida albicans (C. albicans (ATCC: 10231) and found to be good. The cytotoxic potential of Schiff bases was evaluated against MCF-7 cells in terms of IC 50 values [80.19 lM (1) and 44.12 lM (2)] and the results show moderate activity. The anti-tuberculosis activity was the minimum inhibitory concentration (MIC) while screening the anti-tuberculosis activity of 2 was found to be 1.6 lg/mL which is lower than that of the standard drug Pyrazinamide, Streptomycin and Ciprofloxacin. Molecular docking studies were done using molecular operating environment (MOE) program on the 3D structure of the enzymes namely, human thymidylate synthase complexed with DUMP and Raltitrex, Candida albicans N-myristoyltransferasepeptidic inhibitor,
European Journal of Chemistry, 2022
Schiff bases are a proven moiety in antitubercular drug discovery and the antitubercular drug development. Drug discovery is a never-ending process due to evolving drug resistance by the bacteria, as a result, there is a need of developing new antitubercular drugs. In this continuous process of antitubercular drug discovery, new series of Schiff bases are synthesized using quinoline carbohydrazide upon coupling with different aldehydes in ethanolic media through multistep synthesis. These synthesized compounds were purified and characterized by different spectroscopic techniques. The molecules were in vitro screened for antifungal and antibacterial potential by Agar well diffusion assay, antitubercular activity by using microplate Alamar blue assay, and an attempt has been made to study the in-silico relationship between new Schiff base derivatives 4a-f and the crystal structure of M. tuberculosis (5V3Y) protein by molecular docking studies. Synthesized compounds 4a-f show good interaction with the crystal structure of M. tuberculosis protein (5V3Y) and fulfill ADMET characteristics in silico experiments. Among the compounds tested, compound 4d was found to be active against bacteria and fungi. Compound 4b was found to be sensitive against M. tuberculosis at 50 µg/mL concentration. 5V3Y MABA In silico Antifungal activity Multistep synthesis Antibacterial activity
Synthesis, characterization, and anticancer activity of Schiff bases
2019
Five Schiff bases, 2-((3-chlorophenylimino)methyl)-5-(diethylamino)phenol (L1), 2-((2,4-dichlorophenylimino) methyl)-5-(diethylamino)phenol (L2), 5-(diethylamino)-2-((3,5-dimethylphenylimino)methyl)phenol (L3), 2-((2-chloro-4-methylphenylimino)methyl)-5-(diethylamino)phenol (L4), and 5-(diethylamino)-2- ((2,6-diethylphenylimino)methyl)phenol (L5) were synthesized and characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopy. Three of the compounds (L1, L2, and L4) were analyzed by single crystal X-ray diffraction: L1 and L2 crystallized in orthorhombic P212121 and Pca21 space group, respectively, while L4 crystallized in monoclinic P21/c space group. Theoretical investigations were performed for all the synthesized compounds to evaluate the structural details. Drug–DNA interaction studies results from UV–Vis spectroscopy and electrochemistry complement that the compounds bind to DNA through electrostatic interactions. The cytotoxicity of the synthesized compounds was studied against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21) by means of an MTT assay compared to carboplatin, featuring IC50 values in the micromolar range. The pro-apoptotic mechanism for the active compound L5 was evaluated by fluorescence microscopy, cell cycle analysis, caspase-9 and -3 activity, reactive oxygen species production, and DNA binding studies that further strengthen the results of that L5 is a potent drug against cancer.
Zeitschrift fur Naturforschung. C, Journal of biosciences, 2017
A new series of heterocyclic Schiff bases 2-9 containing indole moiety were synthesized by facile and efficient condensation of indole-3/2/5-carboxaldehyde (1a/1b/1c) with different aromatic and heterocyclic primary amines using conventional and/or microwave irradiation methods. The structures of the obtained compounds were assigned by sophisticated spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The synthesized compounds were screened for their cytotoxicity and antibacterial activities. In vitro cytotoxicity screening revealed that compound 5 exhibited moderate activity against KB-3-1 cell line (IC50=57.7 μM) while 5-indolylimino derivative 7 indicated close to the activity (IC50=19.6 μM) in comparison with the positive control (+)-Griseofulvin (IC50=19.2 μM), while the tested compounds 5, 6b, 7 and 9 revealed good or moderate antibacterial activity. In addition, molecular docking study of Schiff bases 2-9 was performed by Molecular Operating Environment (MOE 20...
Royal Society Open Science
A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the DISCOVERY STUDIO 2.5 software, where they showed very interesting ability to intercalate the DNA-topoisomerase complex. Compounds 2a, 2c and 2f showed high docking score values (82.36% −29.98 kcal mol −1 for compound 2a, 78.18% −26.98 kcal mol −1 for compound 2c and 78.65, −28.11 kcal mol −1 for compound 2f) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.
Journal of Chemistry
A new series of p-dimethylaminobenzaldehyde derivatives were tested for therapeutic potential by exploring their properties through characterization. The derivatives were synthesized by 1 : 1 condensation reaction of p-dimethylaminobenzaldehyde and substituted amines. The synthesized compounds 1–8 were characterized by different characterization techniques including IR, mass, 1H NMR, and 13C NMR spectroscopy, elemental analysis, and mass spectrometry. Furthermore, binding of these Schiff bases to Ct-DNA was examined by absorption spectroscopy, fluorescence quenching, circular dichroic, viscosity measurement, molecular docking, and molecular dynamics simulation methods. Schiff bases were tested for antimicrobial activity against bacterial species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus by the disc diffusion method. The pharmacological treatment of Schiff bases showed that 1–8 have promising potential against tested bacterial strains....
Medicinal Chemistry Research, 2016
New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framework has been reported. The structures of the synthesized derivatives were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. The observed MIC values of antitubular activities for the molecule 3a, 3b, 3c, 3d and 3e were 6.25, 3.12, 3.12, 1.60 and 50.0 µg/ml respectively. As compared to ascorbic acid (IC 50 = 62.91 µg/ml), molecule 3a exhibited better antioxidant activities (IC 50 = 36.72 µg/ml). Also, all molecules have shown significant antimicrobial activities. In addition, docking simulations were performed to study ligand-protein interactions and to determine the probable binding conformations. In drug likeness model study compound 3b possessed maximum drug likeness model score (0.75) similar to the standard drug streptomycin. The compound 3a, 3b and 3c were emerged as potential derivatives in the series and could serve as lead compound for the development of potential therapeutic agents.
ChemistrySelect, 2024
The reaction of 2-amino-4,6-dimethylpyridine with 4-cyanobenzaldehyde, salicylaldehyde or 2-hydroxy-1-naphthaldehyde furnished the corresponding N-aryl-(2-pyridyl)aldimines in very good yields. The synthetised Schiff bases were characterized by FT-IR, 1 H, 13 C, DEPT-135 and [ 1 H, 13 C]-HSQC NMR spectroscopy, HRMS and elemental analyses. Additionally, the structure of 2-((E)-(4,6-dimethylpyridin-2-ylimino)methyl)phenol was unambiguously determined by single crystal X-ray diffraction analysis. Hirshfeld analysis of molecular packing was performed. The most common intermolecular interaction is the hydrogenhydrogen (56.8 %) contacts while the most significant interactions are the O…H (6.5 %) and C…C (4.2 %) contacts. DFT calculated geometric parameters and NMR chemical shifts are well correlated with the experimental data. This compound has a net dipole moment of 2.4261 Debye. The MCF-7 growth was suppressed by N-aryl-(2-pyridyl)aldimines more than that for T47D cell line. The IC 50 values of 4-((E)-(4,6-dimethylpyridin-2ylimino)methyl)benzonitrile against MCF-7 and T47D cell lines were the lowest and it is considered the most promising candidate as anticancer agent. Furthermore, this study conducted a molecular docking of benzonitrile-based Schiff base onto DNA duplex to explore a potential molecular mechanism for the robust anticancer activities of this Schiff base adduct. The molecular docking results indicate that benzonitrile-based Schiff base exhibits characteristics of a potential DNA minor groove binder.