scholarly journals Molecular Docking of Lunacridine from Lunasia amara to DNA : Its Inhibition And Interaction Study Correlated With The Cytotoxic Activity on P388 Murine Leukemia Cells

2010 ◽  
Vol 1 (2) ◽  
pp. 108 ◽  
Author(s):  
M. Sulaiman Zubair ◽  
Subehan Subehan
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Cytotoxic Activity ◽  
Topoisomerase Ii ◽  
Leukemia Cells ◽  
Active Principle ◽  
Cytotoxicity Test ◽  
Dna Intercalator ◽  
Ic50 Value ◽  
Murine Leukemia

DNA Topoisomerase II inhibitors are a type of anticancer drugs. These drugs perform their biological activity either by forming a DNA-intercalator-topoisomerase II ternary complex or by inhibiting other enzymes and/or transcription factors that act on DNA. The strong interactions with DNA play a crucial role for their pharmacological properties. Lunacridine, the active principle from Lunasia amara, was known as DNA intercalating Topoisomerase II inhibitor. With the aims to explore the affinity and molecular interaction of lunacridine compound isolated from Lunasia amara with DNA, molecular docking study has been carried out with DNA model using Autodock 4.0 software. Cytotoxicity test on P388 murine leukemia cells was done also using 100, 30, 10, 3 and 1 μg/ml series of lunacridine concentration. The docking result shows that Lunacridine itself could to dock intercalatively between base pairs of DNA and the possibility interaction with adenine, thymine and cytosine by dipole-dipole interaction.  The lowest predicted binding  energy of lunacridine is –6,22 kcal/mol, whereas original ligand bis thiazole is -16,37 kcal/mol. Lunacridine compound itself has less cytotoxic activity on P388 murine leukemia cells with the IC50 value of 39,52 μg/ml or 129,41 μM. The binding energy of lunacridine on DNA higher than original ligand show that the interaction of lunacridine with DNA is not stable afford the less cytotoxic activity. However, based on the IC50 value, lunacridine could be depeloved as anticancer.Key words: docking, lunacridine,  Lunasia amara, cytotoxic, P388 murine leukimia cells.

scholarly journals A Cytotoxic Rocaglate Compound from The Stembark of Aglaia argentea (Meliaceae)

Molekul ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. 146
Author(s):  
Ace Tatang Hidayat ◽  
Kindi Farabi ◽  
Desi Harneti ◽  
Nurlelasari Nurlelasari ◽  
Rani Maharani ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cytotoxic Activity ◽  
Chemical Structure ◽  
Leukemia Cells ◽  
Spectrometric Analysis ◽  
Chemical Marker ◽  
Strong Activity ◽  
Ic50 Value ◽  
Isolated Compound ◽  
Murine Leukemia

The Aglaia genus belong to Meliceae family is unique plant species because the presence of rocaglate and rocaglamide which is so far isolated only from Aglaia genus, indicate that type of this compound as a chemical marker for the genus of Aglaia. This type of compound known to have strong activity, such as insecticide and cytotoxic. This study describe the isolation, structure elucidation, and cytotoxic activity of an isolated rocaglate compound. Dried stembark of A. argentea extracted with methanol and partition between n-hexane, ethyl acetate, and n-butanol, respectively The extracts were tested against P-388 murine leukemia cells and the ethyl acetat showed strongest activity with IC50 value of 15.5 mg/mL. The ethyl acetate then was separated and purified with chromatography technique to obtain isolated compound 1. The chemical structure of isolated  compounds were elucidated by spectroscopic methods including one and two-dimensional NMR as well as high-resolution mass spectrometric analysis and identified as a methyl rocaglate. Compound  1 showed strong cytotoxic activity with an IC50 value of < 0.1 μg/mL.

scholarly journals Diacetate Naphthoquinone Derivatives Tethered to 1,2,3-Triazoles: Synthesis and Cytotoxicity Evaluation in Caco-2 Cells

2021 ◽  
Author(s):  
Dora Costa ◽  
Adriane Francisco ◽  
Beatriz Matuck ◽  
Priscila Furtado ◽  
Alana de Oliveira ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Acetic Anhydride ◽  
Cytotoxic Activity ◽  
Ammonium Nitrate ◽  
Topoisomerase Ii ◽  
Cycloaddition Reaction ◽  
Selectivity Index ◽  
Ceric Ammonium Nitrate ◽  
Metallic Zinc ◽  
Synthetic Route

Acetylated compounds prepared from naphthoquinones have been reported as antitumoral prodrugs. Exploring the synthetic versatility of the naphthoquinone and triazolic nuclei, herein we report a simple and efficient synthetic route to prepare a series of sixteen prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives. The compounds 10a-10h and 11a-11h were obtained by oxidative cycloaddition reaction between lawsone and 4-vinyl-1H-1,2,3-triazoles promoted by ceric ammonium nitrate (CAN) in alkaline medium followed by reductive acetylation of the quinones in excess of metallic zinc and acetic anhydride in yields up to > 98%. All derivatives revealed to be hemocompatible and the compound 11e exhibited the most promising profile against Caco-2 cells showing the higher selectivity index. Molecular docking suggests that these compounds could exert their cytotoxic activity through inhibition of one topoisomerase II isoform, at least.

scholarly journals Combinatorial Library Designing and Virtual Screening of Cryptolepine Derivatives against Topoisomerase II by Molecular Docking

2020 ◽  
Author(s):  
Maria ◽  
Zahid Khan
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Binding Energy ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Combinatorial Library ◽  
Topoisomerase Ii ◽  
Computational Study ◽  
Binding Energies ◽  
Potential Inhibitors

AbstractComputational approaches have emerging role for designing potential inhibitors against topoisomerase 2 for treatment of cancer. TOP2A plays a key role in DNA replication before cell division and thus facilitates the growth of cells. This function of TOP2A can be suppressed by targeting with potential inhibitors in cancer cells to stop the uncontrolled cell division. Among potential inhibitors cryptolepine is more selective and has the ability to intercalate into DNA, effectively block TOP2A and cease cell division in cancer cells. However, cryptolepine is non-specific and have low affinity, therefore, a combinatorial library was designed and virtually screened for identification of its derivatives with greater TOP2A binding affinities.A combinatorial library of 31114 derivatives of cryptolepine was formed and the library was virtually screened by molecular docking to predict the molecular interactions between cryptolepine derivatives and TOP2A taking cryptolepine as standard. The overall screening and docking approach explored all the binding poses of cryptolepine for TOP2A to calculate binding energy. The compounds are given database number 8618, 907, 147, 16755, and 8186 scored lowest binding energies of −9.88kcal/mol, −9.76kcal/mol, −9.75kcal/mol, −9.73kcal/mol, and −9.72kcal/mol respectively and highest binding affinity while cryptolepine binding energy is −6.09kcal/mol. The good binding interactions of the derivatives showed that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of derivatives with different amino acid residues were also observed. A comprehensive understanding of the interactions of proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This Computational study suggests useful references to understand inhibition mechanisms that will help in the modification of TOP2A inhibitors.

scholarly journals SYNTHESIS AND ANTICANCER ACTIVITY TEST OF 2-HYDROXY-N-PHENYLNICOTINAMIDE

2013 ◽  
Vol 13 (2) ◽  
pp. 166-170 ◽  
Author(s):  
Salahuddin Salahuddin ◽  
Muhammad Hanafi ◽  
Hariyanti Hariyanti
Keyword(s):  
Biologically Active ◽  
Leukemia Cells ◽  
Cytotoxicity Test ◽  
The Novel ◽  
Activity Test ◽  
Ic50 Value ◽  
Amidation Reaction ◽  
One Step ◽  
Ft Ir ◽  
The Uk

The novel compound of 2-hydroxy-N-phenylnicotinamide was synthesized from modification of the UK-3A compound, which was known biologically active to inhibit bacterial and cancer cells growth. Synthesis of this compound was carried out in one-step reaction. Analog UK-3A compound namely 2-hydroxy-N-phenylnicotinamide was synthesized from 2-hydroxynicotinic acid as the starting material using amidation reaction with aniline in presence of DCC/DMAP in pyridine. Analog UK-3A was analyzed and identified using TLC, FT-IR, LC-MS and FT-NMR spectrofotometer. The yield after purification was 42.97%. The IC50 value 85 μg/mL was obtained from cytotoxicity test against P388 Murine Leukemia cells. It indicated that the synthesis products were sufficiently potential for leukemia P388 treatment.

scholarly journals Dammarane-Type Triterpenoids from The Stembark of Aglaia argentea (Meliaceae)

2018 ◽  
Vol 4 (1) ◽  
pp. 7-13
Author(s):  
Ace Tatang Hidayat ◽  
Kindi Farabi ◽  
Ida Nur Farida ◽  
Kansy Haikal ◽  
Nurlelasari Nurlelasari ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Spectral Data ◽  
Chemical Structure ◽  
2D Nmr ◽  
Leukemia Cells ◽  
Ic50 Values ◽  
First Time ◽  
Murine Leukemia

Two dammarane-type triterpenoids, 20S,24S-epoxy-3α,25-dihydroxydammarane (1) and 3α-acetyl-20S,24S-epoxy-3α,25-dihydroxydammarane (2), have been isolated from the stembark of Aglaia argentea. The chemical structure of compounds (1 and 2) were identified by spectroscopic evidences including UV, IR, 1D-NMR, 2D-NMR and MS as well as by comparing with previously reported spectral data. Those compounds were isolated from this plant for first time. Compounds (1 and 2) showed cytotoxic activity against P-388 murine leukemia cells with IC50 values of 23.96 and 8.14 mM, respectively.DOI:http://dx.doi.org/10.15408/jkv.v4i1.7065

scholarly journals The study of the apoptogenic effect of pyrimidine derivatives on murine leukemia cells

2005 ◽  
Vol 13 (2) ◽  
pp. 62-64 ◽  
Author(s):  
Galina Gorneva ◽  
Rada Mateva ◽  
Roumyana Gugova ◽  
Evgeny Golovinsky
Keyword(s):  
Cytotoxic Activity ◽  
Morphological Analysis ◽  
Leukemia Cells ◽  
Antitumor Action ◽  
Cytotoxic Action ◽  
Pyrimidine Derivatives ◽  
Apoptotic Morphology ◽  
High Concentrations ◽  
Murine Leukemia

BACKGROUND: In the light of the recent findings concerning the role of apoptosis and of tumor cell enzymes in cancer chemotherapy, the interest in pyrimidine derivatives has greatly increased. Thio- and hydrazine- pyrimidines were synthesized as potential antimetabolites inhibiting the biosynthesis of nucleic acids. Some of them demonstrated biological activity, including antibacterial and antitumor action. The aim of this study was to analyze the cytotoxic activity and the ability of some derivatives to induce apoptosis in murine leukemia cells. METHODS: Exponentially growing cells were incubated with compounds and after 24, 48, and 72 hours were stained with trypan blue and counted hemocytometrically. For detection of the cell fraction undergoing apoptosis, a morphological analysis was made using fluorescent dye propidium iodide. RESULTS: Eight thio- and hydrazine- pyrimidine derivatives were investigated. 2-Thiouracil and 6- hydrazinouracil did not influence the cell growth. 2,4-dithiouracil, 2-thio-4-hydrazinouracil, 2-hydrazinouracil, and 2-thio-5-fluorouracil decreased cell proliferation, but even at the highest studied concentration (1000 ?M) had no cytostatic action. Only high concentrations of 2,4-dihydrazinouracil and 2- chloro-4-hydrazinouracil showed a strong cytotoxic activity. The treatment with 2,4-dihydrazinouracil as well as with 5-fluorouracil caused the appearance of apoptotic cells with typical fragmented condensed nuclei, ghosts and apoptotic bodies. In contrast, dead cells treated with 2-chloro-4-hydrazinouracil did not show apoptotic morphology. CONCLUSION: Among studied eight thio- and hydrazine- pyrimidine derivatives only 2,4-dihydrazinouracil demonstrated strong apoptogenic activity. Its active concentrations were about 100 times higher than apoptogenic concentrations of 5-fluorouracil which points to different mechanisms of cytotoxic action.

scholarly journals 4-Anilino Quinazoline Derivatives: Molecular Docking and Evaluation of In vitro Cytotoxic Activity

2020 ◽  
Vol 11 (4) ◽  
pp. 7559-7564
Author(s):  
Hemalatha K ◽  
Sujatha K ◽  
Panneerselvam P ◽  
Girija K
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Energy ◽  
Cytotoxic Activity ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Quinazoline Derivatives ◽  
Novel Scaffold ◽  
Parp 1

A novel scaffold of 4-anilino quinazoline derivatives was designed on the basis of known inhibitor of quinazoline based drugs. The designed derivatives were synthesized using optimized reaction condition. Their structures were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectral data. The structures of synthesized compounds were subjected to in silico  molecular docking using AutoDock software against the target Poly (ADP-ribose) polymerase-1 (PARP-1) enzyme. The compounds were evaluated for their in vitro cytotoxic activity against Daltons Lymphocyte Ascites (DLA) Cell lines. Molecular docking study of the newly synthesized compounds showed good binding mode in the active site of PARP-1. The docking results were compared with the standard drug Doxorubicin. Doxorubicin showed binding energy of -8.94 kcal/mol and formed one hydrogen bond with Asn767 with a distance of 1.98 Å. Compound SMOQ2 showed the least binding energy, i.e., 11.87kcal/mol and formed one hydrogen bond with Arg 878 with a distance of 1.895.A° Compound DMUQ5 showed binding energy of -11.42 kcal/mol and produced two hydrogen bonds with Arg 878 and Asn 767. Among the synthesized compounds, compounds SMOQ2 and DMUQ5 showed significant binding affinity compared to the standard drug Doxorubicin. The in vitro cytotoxic evaluation indicated that compounds SMOQ2 and DMUQ5 showed significant cytotoxic activity against Daltons Lymphoma Ascites cell line.

scholarly journals Synthesis Methyl Nitrophenyl Acrylate and Cytotoxic Activity Test against P388 Leukemia Cells

2015 ◽  
Vol 15 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Teni Ernawati ◽  
Zulfa Khoirunni’mah
Keyword(s):  
Biological Activity ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
1H Nmr ◽  
13C Nmr ◽  
Leukemia Cells ◽  
P388 Leukemia ◽  
Activity Test ◽  
Murine Leukemia

Synthesis of methyl nitrophenyl acrylate via modification of methyl trans-cinnamate had been done to improve its biological activity. The reaction of methyl trans-cinnamate with nitrating agent gave methyl 3-(2-nitrophenyl)acrylate and methyl 3-(4-nitrophenyl)acrylate with an ortho/para ratio of 1:8. Its structure was confirmed with 1H-NMR, 13C-NMR, FTIR, GC-MS. Biological activity of methyl 3-(4-nitrophenyl)acrylate and methyl 3-(2-nitrophenyl)acrylate assays was performed on Cancer cells against P388 Murine Leukemia with IC50= 7.98 μg/mL, IC50 = 27.78 μg/mL.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

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