scholarly journals Jatrophane Diterpenoids With Protective Effect on Human Lymphocytes DNA

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1984816
Author(s):  
Gordana Krstić ◽  
Milka Jadranin ◽  
Miroslava Stanković ◽  
Ivana Aljančić ◽  
Ljubodrag Vujisić ◽  
...  
Keyword(s):  
Protective Effect ◽  
Human Lymphocytes ◽  
Structural Features ◽  
Positive Control ◽  
Sar Studies ◽  
Structure Activity ◽  
Minimal Dose ◽  
Cbmn Assay ◽  
Sar Study

Two sets of structurally different jatrophanes (1-11 and 13-16), jatrophane 12, and latex extract of 2 Euphorbia species (17 and 18) were tested for in vitro protective effect against chromosome aberrations in peripheral human lymphocytes using the cytokinesis-block micronucleus (CBMN) assay. Jatrophanes 1-6 in minimal doses of 1 µg/mL prominently decreased micronuclei (MN) frequency in the range 44.86% to 34.29% and manifested considerable protective effect. From the other set of jatrophanes, 13 in the same minimal dose notably decreased MN frequency by 31.05%, while extracts 17 and 18 at a concentration of 4 µg/mL remarkably decreased the frequency of MN by 37.94% and 36.12%, respectively. Jatrophanes 12, 14, and 16 showed moderate protection, while 7-11 and 15 were less active than positive control. The structure-activity relationship (SAR) studies of the tested jatrophanes (1-16) indicated the favorable position of benzoate at C-8 or C-9 (3, 4, and 13) and a preference of isobutanoyloxy group at C-3 (1-3) rather than propanoyloxy at the same position (4-6) for pronounced protective effect on human lymphocytes DNA. In a previous SAR study on 11 jatrophanes (1, 3-8, and 13-16), the same structural features in 3, 4, and 13 influenced powerful inhibition of P-gp, while growth inhibition of cancer cells was more than doubled in 1 (isobutanoyloxy group at C-3) compared to 6 (propanoyloxy at C-3).

scholarly journals DNA protective activity of triterpenoids isolated from medicinal mushroom Fomitopsis betulina

2021 ◽  
pp. 39-39
Author(s):  
Ivana Sofrenic ◽  
Boban Andjelkovic ◽  
Ljubodrag Vujisic ◽  
Miroslav Novakovic ◽  
Aleksandar Knezevic ◽  
...  
Keyword(s):  
Protective Effect ◽  
Human Lymphocytes ◽  
Acid Group ◽  
Positive Control ◽  
Dependent Manner ◽  
Protective Activity ◽  
Substitution Pattern ◽  
Concentration Dependent Manner ◽  
Fomitopsis Betulina

Eleven 31-methylenlanostane triterpenoids, i.e. seven 21- and four 26-oic acids, as well as a lupane triterpenoid betulin, isolated from the fruiting bodies of the mushroom Fomitopsis betulina were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin-B blocked micronucleus (CBMN) assay. Most of the tested compounds exerted a beneficial effect by reducing DNA damage of human lymphocytes more effectively than amifostine, a radioprotective agent, used as a positive control. All the tested compounds decreased MN frequency in concentration dependent manner, with the concentration of 2.0 ?g mL-1 being the most effective - with increase of the concentration the activity slightly decreases. The structure-activity relationship (SAR) studies indicated that the lanostanes containing a conjugated 7,9 (11)-diene system exhibit lower activity than D8-analogues. It was also demonstrated that the DNA protective activities within the D8-lanostane-26-oic acid group are affected by 3-substitution pattern. In the D8 series the oxygenation at C-12 or 16 as well as 21- or 26-oic acid functionality proved beneficial for in vitro protective effect on chromosomal aberrations. Betulin exhibited the lowest protective activity, but still comparable to that of amifostine.

scholarly journals Protective Effect on Human Lymphocytes of Some Flavonoids Isolated from Two Achillea Species

2010 ◽  
Vol 5 (5) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Ivana Aljancić ◽  
Miroslava Stanković ◽  
Vele Tešević ◽  
Ljubodrag Vujisić ◽  
Vlatka Vajs ◽  
...  
Keyword(s):  
Protective Effect ◽  
Human Lymphocytes ◽  
Chromosome Breakage ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Proliferation Index ◽  
Chromosome Loss ◽  
Dependent Manner ◽  
Elevated Frequency

This study was conducted to elucidate the in vitro protective effect of five flavonoids [apigenin (1), apigenin-7- O-glucoside (2), centaureidin (3), jaceidin (4) and quercetin (5)] against chromosomal damage in mitogen-induced human lymphocytes. Using the Cytochalasin-B blocked micronucleus (CBMN) assay, in which the biomarker of chromosome breakage and/or chromosome loss is the elevated frequency of micronucleus (MN) in binucleated (BN) cells, the presence of flavonoid 2 in minimal concentration (3 μg/mL) gave a 35.5% decrease in the frequency of MN when compared with control human lymphocytes. The same concentration of flavonoids 1, 3 and 4, reduced the MN frequency by 24.4%, 28.0% and 28.0%, respectively. Higher concentrations (6 μg/mL and 10 μg/mL) seemed less effective. Flavonoid 5 (3 μg/mL) induced a slight decrease in MN frequency (5%), while higher doses (6 μg/mL and 10 μg/mL) provoked an increase of DNA damage. The comparable values for the cytokinesis-block proliferation index (CBPI) of the tested flavonoids and positive control suggested an inhibitory effect on lymphocyte proliferation. In the DPPH. scavenging assay, flavonoids 1-4 demonstrated modest activity, in a dose-dependent manner, compared with the synthetic antioxidants BHT and Trolox, while 5 exhibited comparably high antioxidative activity.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

2020 ◽  
Vol 27 (1) ◽  
pp. 54-77 ◽  
Author(s):  
Bogdan Bumbăcilă ◽  
Mihai V. Putz
Keyword(s):  
Biological Activity ◽  
Wiener Index ◽  
Laboratory Animals ◽  
Covalent Bonds ◽  
Organophosphate Compounds ◽  
Sar Studies ◽  
Structure Activity ◽  
Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

Synthesis, Antimalarial Evaluation and SAR Study of Some 1,3,5-Trisubstituted Pyrazoline Derivatives

2019 ◽  
Vol 16 (10) ◽  
pp. 807-817 ◽  
Author(s):  
Shilpy Aggarwal ◽  
Deepika Paliwal ◽  
Dhirender Kaushik ◽  
Girish Kumar Gupta ◽  
Ajay Kumar
Keyword(s):  
Antimalarial Activity ◽  
Analysis Data ◽  
Docking Study ◽  
Maximum Activity ◽  
Elemental Analysis Data ◽  
Mass Spectral ◽  
Structure Activity ◽  
Pharmacokinetic Properties ◽  
Sar Study

The synthesis of a novel series of 1,3,5-trisubstitiuted pyrazoline was achieved by refluxing chalcone derivative with different heteroaryl hydrazines. The newly synthesized compounds were characterized by 1H NMR, 13CNMR, mass spectral and elemental analysis data. The synthetic series of novel pyrazoline hybrids was screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum. Most of the compounds showed promising in vitro antimalarial activity against CQ sensitive strain. The preliminary structure-activity relationship study showed that quinoline substituted analog at position N-1 showed maximum activity followed by benzothiazole substitution, while phenyl substitution lowers the antimalarial activity. The observed activity was persistent by the docking study on P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.

scholarly journals Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 870
Author(s):  
Joanna Matysiak ◽  
Alicja Skrzypek ◽  
Monika Karpińska ◽  
Kamila Czarnecka ◽  
Paweł Szymański ◽  
...  
Keyword(s):  
Molecular Docking ◽  
High Selectivity ◽  
Antioxidant Properties ◽  
Binding Mode ◽  
Biological Evaluation ◽  
The Other ◽  
Docking Simulations ◽  
Sar Studies ◽  
Structure Activity

In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined. The modified Ellman’s spectrophotometric method was applied for the biological evaluation. The compounds showed strong (IC50 80–90 nM) AChE and moderate (IC50 5–0.2 µM) BuChE inhibition in vitro. Some compounds were effective toward AChE/BuChE, exhibiting high selectivity ratios versus BuChE, while the other compounds were active against both enzymes. The structure–activity relationships were discussed. The compounds inhibited also in vitro self-induced Aβ(1–42) aggregation and exhibited antioxidant properties. The docking simulations showed that the benzimidazoles under consideration interact mainly with the catalytic site of AChE and mimic the binding mode of tacrine.

scholarly journals Synthesis and Antiplasmodial Evaluation of 4-Carboxamido- and 4-Alkoxy-2-Trichloromethyl Quinazolines

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3929
Author(s):  
Dyhia Amrane ◽  
Armand Gellis ◽  
Sébastien Hutter ◽  
Marion Prieri ◽  
Pierre Verhaeghe ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cell ◽  
Alkoxy Group ◽  
Hepg2 Cell Line ◽  
Ccl3 Group ◽  
Falciparum Strain ◽  
Structure Activity ◽  
Trichloromethyl Group ◽  
Sar Study

From three previously identified antiplasmodial hit compounds (A–C) and inactive series (D), all based on a 2-trichloromethylquinazoline scaffold, we conducted a structure-activity relationship (SAR) study at position four of the quinazoline ring by synthesizing 42 novel derivatives bearing either a carboxamido- or an alkoxy-group, to identify antiplasmodial compounds and to enrich the knowledge about the 2-trichloromethylquinazoline antiplasmodial pharmacophore. All compounds were evaluated in vitro for their cytotoxicity towards the HepG2 cell line and their activity against the multiresistant K1 P. falciparum strain, using doxorubicin, chloroquine and doxycycline as reference drugs. Four hit-compounds (EC50 K1 P. falciparum ≤ 2 µM and SI ≥ 20) were identified among 4-carboxamido derivatives (2, 9, 16, and 24) and two among 4-alkoxy derivatives (41 and 44). Regarding the two most potent molecules (16 and 41), five derivatives without a 2-CCl3 group were prepared, evaluated, and appeared totally inactive (EC50 > 50 µM), showing that the 2-trichloromethyl group was mandatory for the antiplasmodial activity.

scholarly journals Synthesis and Antibacterial Evaluation of N-phenylacetamide Derivatives Containing 4-Arylthiazole Moieties

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1772
Author(s):  
Hui Lu ◽  
Xia Zhou ◽  
Lei Wang ◽  
Linhong Jin
Keyword(s):  
Antibacterial Agents ◽  
Antibacterial Activities ◽  
Effective Concentration ◽  
Nematicidal Activity ◽  
Xanthomonas Oryzae ◽  
Membrane Rupture ◽  
Sar Studies ◽  
Structure Activity ◽  
Antibacterial Evaluation

A series of new N-phenylacetamide derivatives containing 4-arylthiazole moieties was designed and synthesized by introducing the thiazole moiety into the amide scaffold. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Their in vitro antibacterial activities were evaluated against three kinds of bacteria—Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac) and X.oryzae pv. oryzicola (Xoc)—showing promising results. The minimum 50% effective concentration (EC50) value of N-(4-((4-(4-fluoro-phenyl)thiazol-2-yl)amino)phenyl)acetamide (A1) is 156.7 µM, which is superior to bismerthiazol (230.5 µM) and thiodiazole copper (545.2 µM). A scanning electron microscopy (SEM) investigation has confirmed that compound A1 could cause cell membrane rupture of Xoo. In addition, the nematicidal activity of the compounds against Meloidogyne incognita (M. incognita) was also tested, and compound A23 displayed excellent nematicidal activity, with mortality of 100% and 53.2% at 500 μg/mL and 100 μg/mL after 24 h of treatment, respectively. The preliminary structure-activity relationship (SAR) studies of these compounds are also briefly described. These results demonstrated that phenylacetamide derivatives may be considered as potential leads in the design of antibacterial agents.

scholarly journals Synthesis and Evaluation of Chirally Defined Side Chain Variants of 7-Chloro-4-Aminoquinoline To Overcome Drug Resistance in Malaria Chemotherapy

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Vasantha Rao Dola ◽  
Awakash Soni ◽  
Pooja Agarwal ◽  
Hafsa Ahmad ◽  
Kanumuri Siva Rama Raju ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Solid State ◽  
Side Chain ◽  
Detailed Structure ◽  
Preclinical Development ◽  
Malaria Parasites ◽  
Sar Studies ◽  
Structure Activity

ABSTRACT A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methylpiperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.

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