scholarly journals Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Assem Barakat ◽  
Hazem A. Ghabbour ◽  
Abdullah Mohammed Al-Majid ◽  
Qurat-ul-ain ◽  
Rehan Imad ◽  
...  
Keyword(s):  
Cell Lines ◽  
Thymidine Phosphorylase ◽  
Fibroblast Cell ◽  
Biological Evaluation ◽  
Molecular Structures ◽  
Butylated Hydroxytoluene ◽  
Normal Fibroblast ◽  
Standard Drug ◽  
X Ray

A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds5a,5d,and5fwere solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds4a,4b,4c,4d,4e,4f, and4gare potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), andN-acetylcysteine. Compounds4a–4e(IC50=101.8±0.8–124.4±4.4 μM) and4g(IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT,IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated,in vitro, against thymidine phosphorylase,α-glucosidase, andβ-glucuronidase enzymes. Compounds4c,4h,4o,4p,4q, 5f,and5mwere found to be potentα-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds4v,and5hwere found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x,4z,and5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except4ywhich was cytotoxic against all the cell lines.

scholarly journals Cavity-Containing [Fe2L3]4+ Helicates: An Examination of Host-Guest Chemistry and Cytotoxicity

2021 ◽  
Vol 9 ◽  
Author(s):  
Lynn S. Lisboa ◽  
Mie Riisom ◽  
Roan A. S. Vasdev ◽  
Stephen M. F. Jamieson ◽  
L. James Wright ◽  
...  
Keyword(s):  
Cell Lines ◽  
Molecular Structures ◽  
Ionization Mass ◽  
Antiproliferative Effects ◽  
X Ray ◽  
X Ray Crystallography ◽  
H Nmr ◽  
Drug Molecules ◽  
Guest Chemistry

Two new di(2,2′-bipyridine) ligands, 2,6-bis([2,2′-bipyridin]-5-ylethynyl)pyridine (L1) and bis(4-([2,2′-bipyridin]-5-ylethynyl)phenyl)methane (L2) were synthesized and used to generate two metallosupramolecular [Fe2(L)3](BF4)4 cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometry, UV-vis, 1H-, 13C and DOSY nuclear magnetic resonance (NMR) spectroscopies. The molecular structures of the [Fe2(L)3](BF4)4 cylinders were confirmed using X-ray crystallography. Both the [Fe2(L1)3](BF4)4 and [Fe2(L2)3](BF4)4 complexes crystallized as racemic (rac) mixtures of the ΔΔ (P) and ΛΛ (M) helicates. However, 1H NMR spectra showed that in solution the larger [Fe2(L2)3](BF4)4 was a mixture of the rac-ΔΔ/ΛΛ and meso-ΔΛ isomers. The host-guest chemistry of the helicates, which both feature a central cavity, was examined with several small drug molecules. However, none of the potential guests were found to bind within the helicates. In vitro cytotoxicity assays demonstrated that both helicates were active against four cancer cell lines. The smaller [Fe2(L1)3](BF4)4 system displayed low μM activity against the HCT116 (IC50 = 7.1 ± 0.5 μM) and NCI-H460 (IC50 = 4.9 ± 0.4 μM) cancer cells. While the antiproliferative effects against all the cell lines examined were less than the well-known anticancer drug cisplatin, their modes of action would be expected to be very different.

scholarly journals Crystal Structure and Biological Evaluation of Two Novel Organic-Inorganic Hybrid Materials as Antitumor Agents in the Treatment of Liver Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Bao-Hua Song ◽  
Chen Li ◽  
Gui-Feng An
Keyword(s):  
Cell Lines ◽  
Hybrid Materials ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Tumor Cell Lines ◽  
Single Crystal Diffraction ◽  
Inorganic Hybrid ◽  
X Ray ◽  
Liver Tumor Cell

Two novel organic-inorganic hybrid materials {(Hbiz)6[AsIII2AsVMoVI18O62]}·H2O (1, biz = benzimidazole) and (dim)[AsIII2AsVMoVI18O62] [2, dim = 1,6-bis(imidazol)hexane] have been successfully obtained by using the molybdenum arsenate and different N donor organic compounds and determined through X-ray single-crystal diffraction technique. The in vitro cytotoxicity of compounds 1 and 2 was then investigated against three human liver tumor cell lines (SMMC7721, Bel-7402, and MHCC97) by MTT assay. It was found that the two compounds showed potent use as antitumor agents against the aforementioned cell lines.

scholarly journals Synthesis, X-ray Analysis, Biological Evaluation and Molecular Docking Study of New Thiazoline Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1654
Author(s):  
Yahia N. Mabkhot ◽  
H. Algarni ◽  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Nabila A. Kheder ◽  
...  
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Biological Evaluation ◽  
Significant Activity ◽  
Inhibition Activity ◽  
Antitumor Activities ◽  
Molecular Docking Study ◽  
X Ray ◽  
Hct 116

A series of new thiazoline derivatives were synthesized. Structure analyses were accomplished employing 1H-NMR, 13C-NMR, X-ray and MS techniques. The in vitro antitumor activities were assessed against human hepatocellular carcinoma (HepG-2) and colorectal carcinoma (HCT-116) cell lines. The results revealed that the thiazolines 5b and 2c exhibited significant activity against the two cell lines. The in vitro antimicrobial screening showed that the thiazolines 2c, 5b and 5d showed promising inhibition activity against Salmonella sp. Additionally, the inhibition activity of thiazolines 2e and 5b against Escherichia coli was comparable to that of the reference compound gentamycin.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

Repositioning of Difluorinated Propanediones as Inhibitors of Histone Methyltransferases and their Biological Evaluation in Human Leukemic Cell Lines

2019 ◽  
Vol 18 (13) ◽  
pp. 1892-1899 ◽  
Author(s):  
Tanushree Pal ◽  
Asmita Sharda ◽  
Bharat Khade ◽  
C. Sinha Ramaa ◽  
Sanjay Gupta
Keyword(s):  
Cell Lines ◽  
Physiological Role ◽  
Leukemic Cell ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Leukemic Cell Lines ◽  
Histone Lysine ◽  
Histone Lysine Methyltransferase ◽  
Subsequent Decrease

Background: At present, ‘pharmaco-epigenomics’ constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process and playing a role in malignancy. Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative to unearth targets to better treat cancer. Here, we intend to repurpose a set of our previously synthesized difluorinated Propanediones (PR) as Histone lysine Methyltransferase inhibitors (HMTi). Methods: The cell lines of leukemic origin viz. histiocytic lymphoma (U937) and acute T-cell leukemia (JURKAT) were treated with PR-1 to 7 after docking studies with active pocket of HMT. The cell cycle analysis, in vitro methylation and cell proliferation assays were carried out to delineate their physiological role. Results: A small molecule PR-4, at 1 and 10µM, has shown to alter the methylation of histone H3 and H4 in both cell lines. Also, treatment shows an increase in G2/M population and a subsequent decrease in the G0/G1 population in U937. In JURKAT, an increase in both G2/M and S phase population was observed. The sub-G1 population showed a steady rise with increase in dose and prolonged time intervals in U937 and JURKAT cell lines. In SRB assay, the PR showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2% in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a potential HMT inhibitor. Conclusion: The molecule PR-4 could be a lead in developing more histone lysine methyltransferases inhibitors with potential to be pro-apoptotic agents.

Survival and Function of Fibroblasts Stored as Stock Cultures at a Non-freezing Temperature

1993 ◽  
Vol 21 (2) ◽  
pp. 206-209
Author(s):  
Anders H. G. Andrén ◽  
Anders P. Wieslander
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Fibroblast Cell ◽  
Freezing Temperature ◽  
Mouse Fibroblast ◽  
Toxic Response ◽  
Normal Manner ◽  
And Function

Cytotoxicity, measured as inhibition of cell growth of cultured cell lines, is a widely used method for testing the safety of biomaterials and chemicals. One major technical disadvantage with this method is the continuous routine maintenance of the cell lines. We decided to investigate the possibility of storing stock cultures of fibroblasts (L-929) in an ordinary refrigerator as a means of reducing the routine workload. Stock cultures of the mouse fibroblast cell line L-929 were prepared in plastic vials with Eagle's minimum essential medium. The vials were stored in a refrigerator at 4–10°C for periods of 7–31 days. The condition of the cells after storage was determined as cell viability, cell growth and the toxic response to acrylamide, measured as cell growth inhibition. We found that the L-929 cell line can be stored for 2–3, weeks with a viabilty > 90% and a cell growth of about 95%, compared to L-929 cells grown and subcultured in the normal manner. The results also show that the toxic response to acrylamide, using refrigerator stored L-929 cells, corresponds to that of control L-929 cells. We concluded that it is possible to store L-929 cells in a refrigerator for periods of up to 3 weeks and still use the cells for in vitro cytotoxic assays.

scholarly journals Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1H-benzo[f]chromene-2-carbonitrile

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 184
Author(s):  
Menna El Gaafary ◽  
Tatiana Syrovets ◽  
Hany M. Mohamed ◽  
Ahmed A. Elhenawy ◽  
Ahmed M. El-Agrody ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Dna Methyltransferase ◽  
Human Cancer ◽  
Theoretical Calculations ◽  
Cancer Cell Lines ◽  
Molecular Structures ◽  
Cytotoxic Activities ◽  
X Ray

The target compound 3-amino-1-(2,5-d ichlorophenyl)-8-methoxy-1H-benzo[f]-chromene-2-carbonitrile (4) was synthesized via a reaction of 6-methoxynaphthalen-2-ol (1), 2,5-dichlorobenzaldehyde (2), and malononitrile (3) in ethanolic piperidine solution under microwave irradiation. The newly synthesized β-enaminonitrile was characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, elemental analysis and X-ray diffraction data. Its cytotoxic activity was evaluated against three different human cancer cell lines MDA-MB-231, A549, and MIA PaCa-2 in comparison to the positive controls etoposide and camptothecin employing the XTT cell viability assay. The analysis of the Hirshfeld surface was utilized to visualize the reliability of the crystal package. The obtained results confirmed that the tested molecule revealed promising cytotoxic activities against the three cancer cell lines. Furthermore, theoretical calculations (DFT) were carried out with the Becke3-Lee-Yang-parr (B3LYP) level using 6-311++G(d,p) basis. The optimization geometry for molecular structures was in agreement with the X-ray structure data. The HOMO-LUMO energy gap of the studied system was discussed. The intermolecular-interactions were studied through analysis of the topological-electron-density(r) using the QTAIM and NCI methods. The novel compound exhibited favorable ADMET properties and its molecular modeling analysis showed strong interaction with DNA methyltransferase 1.

scholarly journals Synthesis and biological evaluation of some novel pyrazolopyrimidines incorporating a benzothiazole ring system

2013 ◽  
Vol 63 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Mohammed Afzal Azam ◽  
Loganathan Dharanya ◽  
Charu Chandrakant Mehta ◽  
Sumit Sachdeva
Keyword(s):  
Antimicrobial Activity ◽  
Diclofenac Sodium ◽  
Biological Evaluation ◽  
Ring System ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Pyrimidine Moiety ◽  
Synthesis And Biological Evaluation

In the present study, a series of benzothiazol derivatives 3a-l containing pyrazolo[3,4-d]pyrimidine moiety at the second position were synthesized and characterized by analytical and spectral data. The compounds were tested for their in vitro antimicrobial activity. Compounds 1-(1,3-benzothiazol-2- yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine (3a), 1- (1,3-benzothiazol-2-yl)-4-(4-chlorophenyl)-3-methyl-1H-pyrazolo[ 3,4-d]pyrimidine (3d) and 1-(1,3-benzothiazol-2-yl)- 3-methyl-4-substituted phenyl-1H-pyrazolo[3,4-d]pyrimidines (3h-j) showed significant inhibitory activity against P. aeruginosa whereas compounds 1-(1,3-benzothiazol-2-yl)-4- (2-chlorophenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3b), 2-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin- 4-yl]phenol (3e), 1-(1,3-benzothiazol-2-yl)-4-(3,4-dimethoxyphenyl)- 3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3h), 4-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyri midin-4-yl]-N,N-dimethylaniline (3j) and 1-(1,3-benzothiazol- 2-yl)-3-methyl-4-[2-phenylvinyl]-1H-pyrazolo[3,4-d]pyrimidine (3k) were found to be active against C. albicans. Some of these synthesized compounds were evaluated for their in vivo acute toxicity, analgesic, anti-inflammatory, and ulcerogenic actions. The tested compound 4-[1-(1,3-benzothiazol- 2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N, N-dimethylaniline (3j) exhibited maximum analgesic and anti-inflammatory activities. Compounds 1-(1,3-benzothiazol- -2-yl)-3-methyl-4-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidine (3i) and 3j showed a significant gastrointestinal protection compared to the standard drug diclofenac sodium.

scholarly journals Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 216 ◽  
Author(s):  
Urszula Majcher ◽  
Greta Klejborowska ◽  
Magdalena Kaik ◽  
Ewa Maj ◽  
Joanna Wietrzyk ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Free Energy ◽  
3D Structure ◽  
Human Tumor ◽  
Biological Evaluation ◽  
Energy Estimates ◽  
Colchicine Derivatives ◽  
Mcf 7

Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin.

scholarly journals A method for identification of vocal fold lamina propria fibroblasts in culture

2008 ◽  
Vol 139 (6) ◽  
pp. 816-822 ◽  
Author(s):  
Susan L. Thibeault ◽  
Wenhua Li ◽  
Stephanie Bartley
Keyword(s):  
Lamina Propria ◽  
Cell Lines ◽  
Von Willebrand Factor ◽  
Vocal Fold ◽  
Fibroblast Cell ◽  
Cytokeratin 19 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Area Of Study

Objective Vocal fold biology research is emerging as a vital area of study in laryngology. One impediment is the lack of both commercially available vocal fold lamina propria fibroblasts and a constitutively expressed specific marker for fibroblasts. We present an in vitro technique that allows for identification of fibroblasts by ruling out the possibility of the cells belonging to other lineages that are found in vocal fold tissue. Study Design An in vitro study. Methods Two primary vocal fold fibroblast cell lines and one immortalized vocal fold fibroblast cell line were cultured. Immunohistologic staining for α-actinin, cytokeratin 19, and von Willebrand factor was completed for the three fibroblast lines in addition to skeletal, endothelial, and epithelial cell lines. Cell type was differentiated by positive staining for α-actinin, cytokeratin 19, and von Willebrand factor. Results Fibroblast cultures did not express α-actinin, cytokeratin 19, and von Willebrand factor, whereas skeletal muscle, endothelial, and epithelial cultured cells expressed each respectively. Conclusions This simple rule-out methodology for fibroblast confirmation is an important step when establishing cell culture, and it establishes sound internal validity particularly in the early stages of this emerging area of study.

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