Antioxidant, cytotoxic activity and pharmacokinetic studies by SwissAdme, Molinspiration, Osiris and DFT of PhTAD-substituted dihydropyrrole derivatives

2021 ◽  
Vol 17 ◽  
Author(s):  
Arif Ayar ◽  
Masuk Aksahin ◽  
Seda Mesci ◽  
Burak Yazgan ◽  
Melek Gül ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Heterocyclic Compounds ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Molecular Structures ◽  
Biologically Active ◽  
Pharmacokinetic Studies ◽  
Ic50 Values ◽  
Mcf 7

Background: Pyrrole compounds having a heterocyclic structure are the most researched and biological activities such as antioxidant and anticancer. Objective: Herein is a first effort to study the significance of heterocyclic compounds to include pyrrole and triazolidine-3,5-dion moiety, on the pharmacokinetic, antioxidant activity and cytotoxic activity on MCF-7 and MCF-12A cell lines. Method: The molecular structures of compounds I-XIV were simulated by the theoretical B3LYP/DFT method. Pharmacokinetic studies of PhTAD-substituted heterocyclic compounds (I-XIV) were analyzed to show Lipinski's rules via in-silico methods of Swiss-ADME. The drug likeness calculations were carried out Molinspiration analyses. The some toxicity risk parameter can be quantified using Osiris. Antioxidant activities determined by DPPH, Fe+2 ions chelating and reducing. Cytotoxic activity measured by MTT and RTCA. Results: Compared with the DPPH activity, the metal chelating activity exhibited serious similar antioxidant effects by PhTAD substituted pyrrole compounds. The same compounds showed the highest activity among the two antioxidant activities. The IC50 values of the compounds are in the range of 12 and 290 µM in MCF-7 cell line. In the MTT and RTCA assays, All compounds showed cytotoxic activity, but about half of the fourteen compounds showed high cytotoxicity. IC50 values of the compounds are in the range of 5 and 54 µM for MTT and range of 1.5 and 44 µM for RTCA. Conclusion: Data of the antioxidant and cytotoxic activity of PhTAD-substituted dihydropyrrole-derived compounds in MCF-7 and MCF-12A cell lines confirmed that the compounds are a biologically active compound and is notable for anti-cancer researches.

scholarly journals Imidazole and carbazole derivatives as potential anticancer agents: molecular docking studies and cytotoxic activity evaluation

2020 ◽  
Vol 34 (2) ◽  
pp. 377-384
Author(s):  
B. Taheri ◽  
M. Taghavi ◽  
M. Zarei ◽  
N. Chamkouri ◽  
A. Mojaddami
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Biological Activities ◽  
Docking Studies ◽  
Carbazole Derivatives ◽  
Ic50 Values ◽  
Docking Energy ◽  
Ht 29 ◽  
Mcf 7

Carbazoles and imidazole represent two important classes of heterocycles which exhibit diverse biological activities such as antitumor properties. In this study, imidazole (C1-C3) and carbazole (C4 and C5) derivatives were evaluated for their cytotoxic activity against three human cancer cell lines namely, MCF7 (human breast cancer), HT29 (human colon cancer), and HeLa (human cervical cancer). Carbazole derivatives (C4 and C5) with IC50 < 10 µM showed greater cytotoxic effect than imidazole derivatives (C1-C3). Furthermore, all compounds exhibited better anticancer activity against MCF-7 than other two cell lines (HT-29, HeLa) and compound C4 was the most potent compound with the IC50 values of 2.5, 5.4 and 4.0 µM, against MCF-7, Hela and HT-29 cell lines, respectively. Physicochemical properties of compounds were calculated and their correlation with the IC50 values on MCF-7 cell line investigated. Surface area and polarizability of compounds showed good correlation by R2 = 0.8396 and R2 = 0.834, respectively. Docking studies of these compounds were also performed on the DNA as proposed target to comprehend their binding interactions and binding energies. The docking energy of compounds ranged from - 11.32 to -13.48 kcal/mol. Compound C3 with energy of -13.48 kcal/mol had the highest docking energy. Docking results indicated that these compounds (C1-C5) had strong affinity in binding to the DNA.                     KEY WORDS: Imidazole, Carbazole, Molecular docking, Cancer, MTT assay   Bull. Chem. Soc. Ethiop. 2020, 34(2), 377-384 DOI: https://dx.doi.org/10.4314/bcse.v34i2.14

Naphthoquinone-based hydrazone hybrids: synthesis and potent activity against cancer cell lines

2020 ◽  
Vol 16 ◽  
Author(s):  
Délis Galvão Guimarães ◽  
Arlan de Assis Gonsalves ◽  
Larissa Araújo Rolim ◽  
Edigênia Cavalcante Araújo ◽  
Victória Laysna dos Anjos Santos ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Biological Activities ◽  
Supporting Electrolyte ◽  
Cancer Cell Lines ◽  
Molecular Structures ◽  
Cytotoxic Activities ◽  
Electrochemical Studies ◽  
Ic50 Values

Background: Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, then the modification at their redox center is an interesting strategy to overcome such harmful activity. Objective: In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β-lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity. Method: The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media. Result: The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, being compounds 3 and 4 the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC50 values in the range 2.90–12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte. Conclusion: These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.

scholarly journals Autophagic Cell Death Is Induced by Acetone and Ethyl Acetate Extracts fromEupatorium odoratum In Vitro: Effects on MCF-7 and Vero Cell Lines

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Faizah Bt. Harun ◽  
Syed Mohsin Syed Sahil Jamalullail ◽  
Khoo Boon Yin ◽  
Zulkhairi Othman ◽  
Anita Tilwari ◽  
...  
Keyword(s):  
Cell Death ◽  
Ethyl Acetate ◽  
Cytotoxic Activity ◽  
Vero Cell ◽  
Cell Lines ◽  
Autophagic Cell Death ◽  
Biologically Active ◽  
Vero Cell Lines ◽  
Mcf 7 ◽  
Ethyl Acetate Extracts

Eupatorium odoratum (EO)contains many biologically active compounds, the anticancer effects of which are not well documented. This study evaluates the cytotoxic effects and mechanism of action ofEOextracts on MCF-7 and Vero cell lines. Evaluation of the cytotoxic activity using MTT assay, morphological alterations, and apoptosis were carried out. Autophagy was evaluated by LC3-A protein expression. Cytotoxic activity, membrane blebbing and ballooning at 24 hours, replacement by mass vacuolation, and double membrane vesicles mimicking autophagy and cell death were observed in the cancer cells. No apoptosis was observed by DNA fragmentation assay. Overexpression of LC3-A protein indicated autophagic cell death. Cell cycle analysis showed G0 and G2/M arrest. The Vero cells did not show significant cell death at concentrations <100 μg/mL. These results thus suggest that acetone and ethyl acetate extracts ofEOinduce cell death through induction of autophagy and hold potential for development as potential anticancer drugs.

scholarly journals Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 830
Author(s):  
Mookho S. Lerata ◽  
Sarah D’Souza ◽  
Nicole R.S. Sibuyi ◽  
Admire Dube ◽  
Mervin Meyer ◽  
...  
Keyword(s):  
Natural Products ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lipid Nanoparticles ◽  
Structural Assignment ◽  
Ic50 Values ◽  
Ht 29 ◽  
Mcf 7

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 μM vs. 8.94 μM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 μM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 μM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

scholarly journals NEW QUINAZOLINONE DERIVATIVES: SYTHESIS AND IN VITRO CYTOTOXIC ACTIVITY

2020 ◽  
Vol 58 (1) ◽  
pp. 12
Author(s):  
Tran Khac Vu
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Cancer Cell Lines ◽  
Ic50 Values ◽  
Quinazolinone Derivatives ◽  
Bioassay Result ◽  
Mcf 7

The paper presents a simple synthesis of new quinazolinone derivatives 13a-i. Synthesized derivatives were tested for their cytotoxic effect against three cancer cell lines including SKLU-1, MCF-7 and HepG-2. The bioassay result showed that only compound 13e exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 9.48, 20.39 and 18.04 µg/ mL, respectively.

scholarly journals Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts

2021 ◽  
Vol 22 (20) ◽  
pp. 11299
Author(s):  
Li Zhang ◽  
Xue-Zhen Feng ◽  
Zhuan-Quan Xiao ◽  
Guo-Rong Fan ◽  
Shang-Xing Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Quaternary Ammonium ◽  
Biological Activities ◽  
Cell Membrane Permeability ◽  
Vitro Assay ◽  
Ic50 Values ◽  
Hct 116 ◽  
Mcf 7

β-pinene is a monoterpene isolated from turpentine oil and numerous other plants’ essential oils, which has a broad spectrum of biological activities. In the current work, six novel β-pinene quaternary ammonium (β-PQA) salts were synthesized and evaluated in vitro for their antifungal, antibacterial and anticancer activities. The in vitro assay results revealed that compounds 4a and 4b presented remarkable antimicrobial activity against the tested fungi and bacteria. In particular, compound 4a showed excellent activities against F. oxysporum f.sp. niveum, P. nicotianae var.nicotianae, R. solani, D. pinea and Fusicoccumaesculi, with EC50 values of 4.50, 10.92, 9.45, 10.82 and 6.34 μg/mL, respectively. Moreover, compound 4a showed the best antibacterial action against E. coli, P. aeruginosa, S. aureus and B. subtilis, with MIC at 2.5, 0.625, 1.25 and 1.25 μg/mL, respectively. The anticancer activity results demonstrated that compounds 4a, 4b, 4c and 4f exhibited remarkable activity against HCT-116 and MCF-7 cell lines, with IC50 values ranged from 1.10 to 25.54 μM. Notably, the compound 4c displayed the strongest cytotoxicity against HCT-116 and MCF-7 cell lines, with the IC50 values of 1.10 and 2.46 μM, respectively. Furthermore, preliminary antimicrobial mechanistic studies revealed that compound 4a might cause mycelium abnormalities of microbial, cell membrane permeability changes and inhibition of the activity of ATP. Altogether, these findings open interesting perspectives to the application of β-PQA salts as a novel leading structure for the development of effective antimicrobial and anticancer agents.

Synthesis, Antiproliferative, and Antioxidant Activities of Substituted N-[(1,3,4-Oxadiazol-2-yl) Methyl] Benzamines

2020 ◽  
Vol 17 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Mohamed Jawed Ahsan ◽  
Lakshya Bhandari ◽  
Shally Makkar ◽  
Rajan Singh ◽  
Mohd. Zaheen Hassan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Drug Concentrations ◽  
Antioxidant Agents ◽  
Ic50 Value ◽  
Mcf 7

Background: Oxadiazole emerged as an important class of heterocyclic compound with diverse biological activities like anticancer, antitubercular, anticonvulsant, anti-tubulin, antimicrobial, anti-inflammatory, antioxidant etc. Objective: The objective of this study is to synthesis series of twelve substituted N-[(1,3,4-oxadiazol-2- yl)methyl]benzamines (6a-l) and their evaluation as antiproliferative and antioxidant agents. Methods: The substituted N-[(1,3,4-oxadiazol-2-yl)methyl]benzamines (6a-l) analogues were synthesized as per the reported procedure. The antiproliferative activity was tested against nine different panels cancer cell lines (leukemia, colon, renal, non-small cell lung, breast, CNS, melanoma, prostate, and ovarian cancer) at 10 µM drug concentrations as per the NCI US Protocol. Results: 2-(5-((3-Chloro-4-fluorophenylamino)methyl)-1,3,4-oxadiazol-2-yl)phenol (6e) revealed the significant antiproliferative activity among the series of title compounds (6a-l). The compound, 6e showed maximum sensitivity towards CCRF-CEM, MCF-7, MOLT-4, T-47D, and SR cell lines with percent growth inhibitions (%GIs) of 79.92, 56.67, 39.62, 34.71 and 33.35, respectively. Furthermore, the compounds, 6e and 6c showed promising antioxidant activity with an IC50 value of 15.09 and 19.02 µM, respectively in DPPH free radicals (FR) scavenging activity.R Conclusion: The present study may support a significant value in cancer drug discovery programme.

Benzo[α]phenoxazines and benzo[α]phenothiazine from vitamin K3: synthesis, molecular structures, DFT studies and cytotoxic activity

RSC Advances ◽  
2015 ◽  
Vol 5 (71) ◽  
pp. 57917-57929 ◽  
Author(s):  
Dattatray Chadar ◽  
Soniya S. Rao ◽  
Ayesha Khan ◽  
Shridhar P. Gejji ◽  
Kiesar Sideeq Bhat ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Topoisomerase Ii ◽  
Molecular Structures ◽  
Dft Studies ◽  
Vitamin K3 ◽  
Topoisomerase Ii Inhibitors ◽  
Mcf 7

Novel benzo[α]phenoxazines and benzo[α]phenothiazine from vitamin K3 are cytotoxic against HeLa, MCF-7 cell lines and potential topoisomerase II inhibitors.

scholarly journals Isolation, Characterization, Complete Structural Assignment, and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5827
Author(s):  
Hamdoon A. Mohammed ◽  
Mohammed F. Abd El-Wahab ◽  
Usama Shaheen ◽  
Abd El-Salam I. Mohammed ◽  
Ashraf N. Abdalla ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Structure Characterization ◽  
Lung Fibroblasts ◽  
Flavonoid Glycosides ◽  
Isolation And Purification ◽  
Ic50 Values ◽  
Mcf 7

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC50 values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC50 values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.

scholarly journals A Comparison of the Cytotoxic Activity of Extracts from Artificial Fruiting Bodies and Mycelial Biomass of Cordyceps neovolkiana (DL004) Fungus

2018 ◽  
Vol 56 (4A) ◽  
pp. 53
Author(s):  
Dũng Chí Nguyễn
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
National Parks ◽  
Jurkat Cell ◽  
Fruit Body ◽  
Jurkat Cells ◽  
Parasitic Fungus ◽  
Composition Analysis ◽  
Ic50 Values ◽  
Mcf 7

ABSTRACTC-HCTN-69Cordyceps neovolkiana is an insect-parasitic fungus, naturally distributed in the Langbiang mountain, Tam Dao and Ba Vi national parks of Vietnam. This study assessed and compared the in vitro cytotoxic activity of crude extracts from fruit bodies and biomass of artifical C. neovolkiana fungus against human Jurkat (acute T cell leukemia) and breast carcinoma (MCF-7) cells using the sulforhodamine B (SRB) assay. We obtained the extracts via the ethanol extraction and liquid-liquid extraction with four different solvents; ethanol (EtOH) petroleum ether (60 – 80oC) (PE), etyl acetate (ET), butanol (BU) and water (W), successively. The result shows both the cytotoxic potential of biomass and fruit-body extracts were determined the IC50 value at 0 – 100 µg/mL concentration. The PE-fruit-body extract displayed the highest cytotoxic activity on MCF-7 and Jurkat cell lines with IC50 values of 76,30 ± 1,20 µg/mL and 37,18 ± 1,39 µg/mL, respectively. Beside that, the PE- biomass extracts respectively showed the highest cytotoxic activity on MCF-7 and Jurkat cell lines with IC50 values of 26,94 ± 1,62 µg/mL and 15,50 ± 0,19. Obviously, we need to study further about the cytotoxic mechanism PE-fruit-body and biomass extracts on MCF-7 and Jurkat cells and chemical composition analysis of extracts to possibly use as a promising anticancer agent.  

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