Structural requirements of salicylaldehyde benzoylhydrazones and their Cu(II) complexes for anticancer activity

Salicylaldehyde benzoylhydrazone (H2sb) has a variety of biological activities including anticancer activity. The Cu(II) complexes of H2sbs possess enhanced anticancer activity as compared with their free ligands. A quantitative structure–activity relationship (QSAR) analysis was performed on a series of H2sb ligands and their corresponding Cu(II) complexes to capture the structural requirements that are responsible for the bioactivity. The predictive QSAR models were developed using statistical techniques such as multiple linear regression (MLR) and principal component regression analysis (PCRA). We used different combinations of various descriptors such as a physicochemical descriptor, electrotopological state atom (ETSA) indices, and descriptors derived from density functional theory (DFT) calculations. The DFT-derived descriptors used for QSAR analysis are HOMO and LUMO energies, atomic charges, chemical potential, and hardness. Our developed models showed the importance of the lipophilicity index (ClogP), ETSA indices, and atomic charges for anticancer activities of the H2sb analogs and their Cu(II) complexes. In addition, our MLR models revealed that, while the global lipophilicity index and hardness are important for anticancer activity of H2sb ligands, chemical potential and HOMO energy are important for the anticancer activity of Cu(II) complexes.

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Partial Characterization, the Immune Modulation and Anticancer Activities of Sulfated Polysaccharides from Filamentous Microalgae Tribonema sp.

Molecules ◽

10.3390/molecules24020322 ◽

2019 ◽

Vol 24 (2) ◽

pp. 322 ◽

Cited By ~ 15

Author(s):

Xiaolin Chen ◽

Lin Song ◽

Hui Wang ◽

Song Liu ◽

Huahua Yu ◽

...

Keyword(s):

Anticancer Activity ◽

Hepg2 Cells ◽

Immune Modulation ◽

Biological Activities ◽

Interleukin 10 ◽

Biofuel Production ◽

Sulfated Polysaccharides ◽

Anticancer Activities ◽

Macrophage Cells

Recently, Tribonema sp., a kind of filamentous microalgae, has been studied for biofuel production due to its accumulation of triacylglycerols. However, the polysaccharides of Tribonema sp. and their biological activities have rarely been reported. In this paper, we extracted sulfated polysaccharides from Tribonema sp. (TSP), characterized their chemical composition and structure, and determined their immunostimulation and anticancer activities on RAW264.7 macrophage cells and HepG2 cells. The results showed that TSP is a sulfated polysaccharide with a Mw of 197 kDa. TSP is a heteropolysaccharide that is composed mainly of galactose. It showed significant immune-modulatory activity by stimulating macrophage cells, such as upregulating interleukin 6 (IL-6), interleukin 10 (IL-10), and tumor necrosis factor α (TNF-α). In addition, TSP also showed significant dose-dependent anticancer activity (with an inhibition rate of up to 66.8% at 250 µg/mL) on HepG2 cells as determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cycle analysis indicated that the anticancer activity of TSP is mainly the result of induced cell apoptosis rather than affecting the cell cycle and mitosis of HepG2 cells. These findings suggest that TSP might have potential as an anticancer resource, but further research is needed, especially in vivo experiments, to explore the anticancer mechanism of TSP.

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Theoretical Investigation on Biological Activity of Imidazole Derivatives [Carbenzim, Mebendazole] by using (DFT) and (PM3) Methods

Al-Nahrain Journal of Science ◽

10.22401/anjs.24.2.01 ◽

2021 ◽

Vol 24 (2) ◽

pp. 1-8

Author(s):

Amar Tuma Musa ◽

◽

Khalida Abaid ◽

Keyword(s):

Density Functional ◽

Chemical Potential ◽

Theoretical Study ◽

Chemical Reactivity ◽

Biological Activities ◽

Biological Properties ◽

Benzimidazole Derivatives ◽

Log P ◽

P Value ◽

Reactivity Descriptors

The theoretical study represents an essential preliminary stage for the start of any industry, as it gives a theoretical description of the properties of compounds (chemical, physical and biological properties)without conducting research to find out about this and the least cost. Through the theoretical study, we extract a clear picture of the chemical compounds before starting to manufacture them to know the extent of their impact on human health and their chemical and biological effectiveness. Using the Density Functional Theory (DFT/B3LYP) with base 6-311G,throughGaussian 09 program, the optimize geometry,(bond lengths, angles bond)and vibrational spectra was calculated of the benzimidazole derivatives [Carbenzim (CZM), Mebendazole (MBZ)].Through orbital charts of HOMO and LUMO to study electronic properties. The HOMO-LUMO gap was also evaluated for chemical reactivity and determination of global reactivity descriptors (Hardness (),Softness (S), Electrophilicity(), Chemical potential(),Electronegativity(χ))] that defines compunds effectiveness and the their biological activities. In addition, (QSAR) data has been used to develop relationships between biological activities and thermophysical properties of chemicals, through the Hyper Chem8.0programbyusingSemi-empirical(SE)method at the (PM3) level. The LOG P value was calculated, binding energy, Polarizability, hydration energy, surface area, and electrostatic potential energy difference of two level.

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Biotransformation of oleic acid and antimicrobial and anticancer activities of its biotransformatıon extracts

Bulgarian Chemical Communications ◽

10.34049/bcc.51.2.4831 ◽

2019 ◽

Vol 51 (2) ◽

pp. 200-205

Author(s):

Ö. Özşen Batur ◽

Ö. Atlı ◽

İ. Kıran

Keyword(s):

Oleic Acid ◽

Anticancer Activity ◽

Cell Line ◽

Clinical Isolate ◽

Alternaria Alternata ◽

Edible Oils ◽

Biological Activities ◽

Anticancer Activities ◽

Ic50 Value

Oleic acid is an unsaturated fatty acid found in significant quantities in various edible oils. Scientific studies have shown that oleic acid and its derivatives exhibit a variety of biological activities including antimicrobial and anticancer activities. In the present work, biotransformation of oleic acid was carried out initially using 27 different microbial strains. Extracts obtained from biotransformation with Alternaria alternata (clinical isolate) and Aspergillus terreus var. africanus (clinical isolate) were used in antimicrobial and anticancer activity studies. The in vitro antimicrobial activities of the extracts were evaluated against 9 different pathogenic microorganisms. The results indicated that the microbial extracts were more active than oleic acid itself and showed good inhibitory activity against all tested microorganisms. In in vitro anticancer activity studies, extract 2 obtained from biotransformation with Alternaria alternata exhibited notable anticancer activity against A549 cell line with an IC50 value of 62.5 μg/ml whereas positive control cisplatin showed an IC50 value of 43.5 μg/ml. The anticancer activity of extract 2 was also found to be selective according to its higher IC50 value (122.7 μg/ml) obtained against the healthy cell line, mouse embryonic fibroblasts, NIH3T3. Due to its anticancer effect, extract 2 is considered to participate in further research.

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Atomic charges for conformationally rich molecules obtained through a modified principal component regression

Physical Chemistry Chemical Physics ◽

10.1039/c7cp05703b ◽

2018 ◽

Vol 20 (4) ◽

pp. 2890-2903 ◽

Cited By ~ 1

Author(s):

Tymofii Yu. Nikolaienko ◽

Leonid A. Bulavin

Keyword(s):

Dipole Moment ◽

Potential Energy ◽

Potential Energy Surface ◽

Regression Model ◽

Energy Surface ◽

Principal Component Regression ◽

Principal Component ◽

Atomic Charges ◽

Local Minima ◽

Fixed Set

A modification of the principal component regression model is proposed for obtaining a fixed set of atomic charges (referred to as dipole-derived charges) optimized for reproducing the dipole moment of a conformationally rich molecule, i.e., a molecule with multiple local minima on the potential energy surface.

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Quantitative Structure–Activity Relationship Studies of Anticancer Activity for Isatin (1H-indole-2,3-dione) Derivatives Based on Density Functional Theory

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2017070108 ◽

2017 ◽

Vol 2 (2) ◽

pp. 90-115 ◽

Cited By ~ 1

Author(s):

Samir Chtita ◽

Mounir Ghamali ◽

Majdouline Larif ◽

Rachid Hmamouchi ◽

Mohammed Bouachrine ◽

...

Keyword(s):

Anticancer Activity ◽

Density Functional ◽

Nonlinear Models ◽

Principal Component ◽

Quantitative Structure Activity Relationship ◽

Multivariate Statistical ◽

Predicted Values ◽

Validation Tests ◽

New Compounds ◽

Isatin Derivatives

To establish a QSAR of anticancer activity for Isatin derivatives, a series of Isatin derivatives were analyzed by principal component analysis, multiple linear regression, partial least squares and multiple nonlinear regression analysis. The authors proposed linear and nonlinear models and interpreted the activity of the compounds by multivariate statistical analysis. The proposed models were used to predict the activity of test set compounds, and an agreement between experimental and predicted values was verified. The applicability domain of MLR models was investigated using William's plot to detect outliers and outsides compounds. For the successful application of the developed models to predict new compounds, rigorous validation tests have been used in this direction. Additionally, the rm2 metrics have been used to ensure the close agreement of predicted response data with observed ones. The developed models have been used for designing some new Isatin derivatives with high predicted values of anticancer effect.

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Synthesis and Anticancer Activities of 4-[(Halophenyl)diazenyl]phenol and 4-[(Halophenyl)diazenyl]phenyl Aspirinate Derivatives against Nasopharyngeal Cancer Cell Lines

Journal of Chemistry ◽

10.1155/2017/6760413 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Boon Kui Ho ◽

Zainab Ngaini ◽

Paul Matthew Neilsen ◽

Siaw San Hwang ◽

Reagan Entigu Linton ◽

...

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Cultured Cells ◽

Colorimetric Assay ◽

Biological Activities ◽

Nasopharyngeal Cancer ◽

Coupling Reaction ◽

Basic Solution ◽

Anticancer Activities ◽

Low Cytotoxicity

Aspirin and azo derivatives have been widely studied and have drawn considerable attention due to diverse biological activities. In this study, a series of 4-[(halophenyl)diazenyl]phenyl aspirinate derivatives were synthesized from the reaction of aspirin with 4-[(halophenyl)diazenyl]phenol via esterification, in the presence of DCC/DMAP in DCM with overall yield of 45–54%. 4-[(Halophenyl)diazenyl]phenol was prepared prior to esterification from coupling reaction of aniline derivatives and phenol in basic solution. All compounds were characterized using elemental analysis, FTIR, and 1H and 13C NMR spectroscopies. All compounds were screened for their anticancer activities against nasopharyngeal cancer (NPC) HK-1 cell lines and the viability of cultured cells was determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxylphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]-based colorimetric assay. 4-[(E)-(Fluorophenyl)diazenyl]phenol showed the highest anticancer activity against NPC HK-1 cell lines compared to other synthesized compounds. 4-[(Halophenyl)diazenyl]phenyl aspirinate showed low cytotoxicity against NPC HK-1 cell lines compared to 4-[(halophenyl)diazenyl]phenol but better anticancer activity than aspirin alone.

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QUANTITATIVE ELECTRONIC STRUCTURE - ACTIVITY RELATIONSHIPS ANALYSIS ANTIMUTAGENIC BENZALACETONE DERIVATIVES BY PRINCIPAL COMPONENT REGRESSION APPROACH

Indonesian Journal of Chemistry ◽

10.22146/ijc.21876 ◽

2010 ◽

Vol 4 (1) ◽

pp. 68-75

Author(s):

Yuliana Yuliana ◽

Harno Dwi Pranowo ◽

Jumina Jumina ◽

Iqmal Tahir

Keyword(s):

Electronic Structure ◽

Latent Variables ◽

Principal Component Regression ◽

Theoretical Data ◽

Principal Component ◽

Antimutagenic Activity ◽

Statistical Parameters ◽

Qsar Analysis ◽

Structure Activity ◽

Net Charges

Quantitative Electronic Structure Activity Relationship (QSAR) analysis of a series of benzalacetones has been investigated based on semi empirical PM3 calculation data using Principal Components Regression (PCR). Investigation has been done based on antimutagen activity from benzalacetone compounds (presented by log 1/IC50) and was studied as linear correlation with latent variables (Tx) resulted from transformation of atomic net charges using Principal Component Analysis (PCA). QSAR equation was determinated based on distribution of selected components and then was analysed with PCR. The result was described by the following QSAR equation : log 1/IC50 = 6.555 + (2.177).T1 + (2.284).T2 + (1.933).T3 The equation was significant on the 95% level with statistical parameters : n = 28 r = 0.766 SE = 0.245 Fcalculation/Ftable = 3.780 and gave the PRESS result 0.002. It means that there were only a relatively few deviations between the experimental and theoretical data of antimutagenic activity. New types of benzalacetone derivative compounds were designed and their theoretical activity were predicted based on the best QSAR equation. It was found that compounds number 29, 30, 31, 32, 33, 35, 36, 37, 38, 40, 41, 42, 44, 47, 48, 49 and 50 have a relatively high antimutagenic activity. Keywords: QSAR; antimutagenic activity; benzalaceton; atomic net charge

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Electronic and structural computing features of some chromene derivatives and evaluating their anticancer activities

Main Group Chemistry ◽

10.3233/mgc-210136 ◽

2021 ◽

pp. 1-8

Author(s):

Setareh Azimzadeh-Sadeghi

Keyword(s):

Amino Acids ◽

Anticancer Activity ◽

Molecular Orbital ◽

Density Functional ◽

Energy Levels ◽

Structural Features ◽

Binding Energies ◽

Original Structure ◽

Anticancer Activities ◽

Other Substances

Electronic and structural features of some of representative chromene derivatives were investigated in this work towards recognizing their anticancer roles. Density functional theory (DFT) calculations were performed to obtain five structures of chromene derivatives with the same skeleton of original structure. In addition to obtaining optimized structural geometries, electronic molecular orbital features were evaluated for the models. Energy levels of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) indicated effects of additional R group pf chromene derivatives on electronic features. Based on such results, it was predicted that one of derivatives, L5, could better participate in interactions with other substances in comparison with other ligand structures. This achievement was obtained based on availability of HOMO and LUMO levels in lower energies easily catchable for electron transferring. On the other hand, L5 was assumed to interact in the weakest mode with other substances. Indeed, the main goal of this work was to examine anticancer activity of the investigated chromene derivatives, in which each of L1–L5 chromene derivatives were analyzed first to recognized electronic and structural features. Next, molecular docking (MD) simulations were performed to examine anticancer role of L1–L5 against methyltransferase cancerous enzyme target. The results indicated that formations of ligand-target complexes could be occurred within different types of interactions and surrounding amino acids of central ligand. In agreement with the achievements of analyses of single-standing L1–L5 compounds, L4-Target was seen as the strongest complex among possible complex formations. Moreover, values of binding energies and inhibition constant indicated that all five chromene derivatives could work as inhibitors of methyltransferase cancerous enzyme by the most advantage for L4 ligand. And as a final remark, details of such anticancer activity were recognized by graphical representations of ligand-target complexes showing types of interactions and involving amino acids in interactions.

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Anticancer activities of bovine and human lactoferricin-derived peptides

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0175 ◽

2017 ◽

Vol 95 (1) ◽

pp. 91-98 ◽

Cited By ~ 36

Author(s):

Mauricio Arias ◽

Ashley L. Hilchie ◽

Evan F. Haney ◽

Jan G.M. Bolscher ◽

M. Eric Hyndman ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Mononuclear Cells ◽

Biological Activities ◽

Cell Penetrating Peptides ◽

Jurkat Cells ◽

Mammalian Host ◽

Anticancer Activities ◽

Normal Peripheral Blood ◽

Cell Penetrating

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly–Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

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Structure, Stability and Water Adsorption on Ultra-Thin TiO2 Supported on TiN

10.26434/chemrxiv.8425367.v1 ◽

2019 ◽

Author(s):

Jose Julio Gutierrez Moreno ◽

Marco Fronzi ◽

Pierre Lovera ◽

alan O'Riordan ◽

Mike J Ford ◽

...

Keyword(s):

Density Functional ◽

Water Adsorption ◽

Chemical Potential ◽

Energy Gap ◽

Molecular Water ◽

Structure Stability ◽

Ambient Conditions ◽

Rutile Structure ◽

The Stability ◽

The One

Interfacial metal-oxide systems with ultrathin oxide layers are of high interest for their use in catalysis. In this study, we present a density functional theory (DFT) investigation of the structure of ultrathin rutile layers (one and two TiO2 layers) supported on TiN and the stability of water on these interfacial structures. The rutile layers are stabilized on the TiN surface through the formation of interfacial Ti–O bonds. Charge transfer from the TiN substrate leads to the formation of reduced Ti3+ cations in TiO2. The structure of the one-layer oxide slab is strongly distorted at the interface, while the thicker TiO2 layer preserves the rutile structure. The energy cost for the formation of a single O vacancy in the one-layer oxide slab is only 0.5 eV with respect to the ideal interface. For the two-layer oxide slab, the introduction of several vacancies in an already non-stoichiometric system becomes progressively more favourable, which indicates the stability of the highly non-stoichiometric interfaces. Isolated water molecules dissociate when adsorbed at the TiO2 layers. At higher coverages the preference is for molecular water adsorption. Our ab initio thermodynamics calculations show the fully water covered stoichiometric models as the most stable structure at typical ambient conditions. Interfacial models with multiple vacancies are most stable at low (reducing) oxygen chemical potential values. A water monolayer adsorbs dissociatively on the highly distorted 2-layer TiO1.75-TiN interface, where the Ti3+ states lying above the top of the valence band contribute to a significant reduction of the energy gap compared to the stoichiometric TiO2-TiN model. Our results provide a guide for the design of novel interfacial systems containing ultrathin TiO2 with potential application as photocatalytic water splitting devices.

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