Synthesis, cytotoxicity and in silico study of some novel benzocoumarin-chalcone-bearing aryl ester derivatives and benzocoumarin-derived arylamide analogs

2021 ◽  
Vol 76 (3-4) ◽  
pp. 201-210
Author(s):  
Nabeel A. Abdul-Ridha ◽  
Afraah D. Salmaan ◽  
Rita Sabah ◽  
Bahjat Saeed ◽  
Najim A. Al-Masoudi
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Hydrophobic Interactions ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Protein Receptor ◽  
Normal Human Liver ◽  
Normal Human

Abstract The development of new prostate cancer protein receptor cytochrome P450 17A1 inhibitors offers the possibility of generating structures of increased potency. To this end, the chalcone analogs 7 and 8 were prepared from treatment of methyl 3-oxo-3H-benzocoumarin-2-carboxylate (4) with aryl aldehydes. Treatment of 7 and 8 with three anti-inflammatory drugs, flurbiprofen, ketoprofen and ibuprofen, in the presence of POCl3/DMAP gave the ester analogs 9–12. Analogously, treatment of ethyl 3-oxo-3H-benzocoumarin-2-carboxylate (15), prepared previously from 2-hydroxy-1-naphthaldehyde (13) and dimethylmalonate (14), with various arylamines: 4-bromoaniline, 2-amino-6-methylpyridine, amino-antipyrine and 2-amino-5-nitrothiazole, in the presence of potassium tert-butoxide gave the benzocoumarine-3-arylamide analogs. The in vitro cytotoxic activities of 9–12 and 16–19 were evaluated against human prostate cancer cell lines (PC-3) and normal human liver epithelia (WRL-68) by MTT assay. Compounds 10 and 17 were the most active cytotoxic agents among the series against PC-3 cells with IC50 values of 71.35 and 78.25 μg mL–1 with SI values of 3.0 and 4.2, respectively (calculated from the cytotoxicity effects of 10 and 17 on the normal human liver epithelia [WRL-68]). Furthermore, compounds 11 and 12 were tested against breast cancer (HER2 cell lines), prostate cancer (DU-135 cell lines) and MCF-7 but were inactive. Molecular docking studies between the protein receptor CYPP450 17A1 and compounds 10 and 17 revealed that these compounds primarily form hydrophobic interactions with the receptor.

Ru(III) complexes of pyrazolopyrimidines as anticancer agents: In vitro, in vivo anticancer activity and underlying multi-mechanisms

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Wen-Ying Shen ◽  
Qi-Yuan Yang ◽  
Zhen-Feng Chen ◽  
Hong Liang
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human ◽  
Low Toxicity

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(Ln)(H2O)Cl3] (13, n=13) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver...

One-Pot Synthesis of 5-(Het)Aryl 8-Aminoquinoline Amide Derivatives as Potential Antibacterial / Cytotoxic Agents

2020 ◽  
Vol 16 (2) ◽  
pp. 142-151
Author(s):  
Zanjam Spandana ◽  
Tadigiri M. Rekha ◽  
Mandava V.B. Rao ◽  
Manojit Pal
Keyword(s):  
Hepg2 Cell ◽  
Cell Lines ◽  
Antibacterial Activities ◽  
Cytotoxic Agents ◽  
Hek293 Cells ◽  
Cytotoxic Activities ◽  
Quinoline Derivatives ◽  
One Pot ◽  
Hepg2 Cell Lines

Background: The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Dehydrogenase (G6PD) Activity. The 4-aryl- 8-amino(acetamido)quinoline derivatives, on the other hand, have shown antiproliferative activities against cancer cell lines. These reports prompted us to assess the antibacterial and cytotoxic activities of a series of compounds based on 5-aryl 8-aminoquinoline amide scaffold. Methods: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized via a one-pot ultrasound-assisted method using a C-5 selective halogenation of quinoline derivatives followed by Pd/C-catalyzed Suzuki-Miyaura coupling with (het)aryl boronic acids. All these compounds were evaluated for their in vitro antibacterial activities against representative Gram-(+) and Gram-(-) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Staphylococcus aureus. Three compounds were further tested for cytotoxicities in vitro against breast adenocarcinoma (MCF7) and Hepatocellular Carcinoma (HepG2) along with non-cancerous human embryonic kidney (HEK293) cell lines. Results: All these compounds demonstrated moderate to good antibacterial activities against the four organisms used. In vitro assay results revealed that three compounds showed good activities against Gram-(+) strains and Gram-(-) strains and one was comparable to ciprofloxacin and pefloxacin. These three compounds were further tested for their cytotoxic properties against MCF7 and HepG2 cell lines. One of them showed IC50 value comparable to doxorubicin when tested against HepG2 cell lines. However, none of these compounds showed any significant effects when tested against HEK293 cells indicating their selectivity towards the growth inhibition of cancer cells. Conclusion: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized and evaluated for antibacterial and cytotoxic activities. Several of these compounds showed promising antibacterial and cytotoxic activities when tested in vitro suggesting that the present class of compounds may be of interest for the identification of new and potential antibacterial / cytotoxic agents.

scholarly journals Studies of in vitro anti-prostate cancer potential of newer 1,2,4-triazolo-1,3,4-thiadiazines with different heteroaromatics

2015 ◽  
Vol 10 (2) ◽  
pp. 308 ◽  
Author(s):  
Mao-Chuan Fan ◽  
Guang-Ye Han ◽  
Xin-Jun Zhang ◽  
Hui-Fang Xi
Keyword(s):  
Prostate Cancer ◽  
Nmr Spectroscopy ◽  
Cell Lines ◽  
Prostate Cancer Cell ◽  
Cytotoxic Agents ◽  
Prostate Cancer Cell Lines ◽  
H Nmr ◽  
Ft Ir ◽  
C Nmr

<p>This study was aimed to evaluate anticancer potential of newer synthesize 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines and its derivatives. All newly furnished scaffolds were subjected to screening for their in vitro anticancer potential against DU-145 and PC-3 prostate cancer cell lines using SRB and MMT bioassays. The structures of final compounds were confirmed with the aid of FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR spectroscopy and CHN analysis. Bioassay studies suggested that all thiadiazines were promising cytotoxic agents with % cytotoxicity ranging from 44.39-71.24%, whereas potent GI<sub>50</sub> level in the range 11.96-32.51 µg/mL and results were comparable to the potencies of control drugs adriamycin and doxorubicin. Variation of heterocyclic pharmacophores along with the C-5 position of 1,2,4-triazole in terms of quinoline, quinazoline, coumarin and pyridine lead to the different SAR predictions in which quinoline and benzimidazole moieties found most promising.</p><p> </p>

Effect of l-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo

1992 ◽  
Vol 83 (2) ◽  
pp. 183-190 ◽  
Author(s):  
P. C. Dagnelie ◽  
D. K. Menon ◽  
I. J. Cox ◽  
J. D. Bell ◽  
J. Sargentoni ◽  
...  
Keyword(s):  
Body Weight ◽  
Human Liver ◽  
Pulse Sequence ◽  
Whole Body ◽  
Maximal Increase ◽  
Normal Human Liver ◽  
Normal Human ◽  
Biochemical Pathology

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters]. 5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.

Synthesis and Evaluation of Aromatic Surfactants as Potential Antibacterial and Cytotoxic Agents

2019 ◽  
Vol 16 (6) ◽  
pp. 478-484
Author(s):  
Kenia Barrantes ◽  
Mary Fuentes ◽  
Luz Chacón ◽  
Rosario Achí ◽  
Jorge Granados-Zuñiga ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Hela Cells ◽  
Cytotoxic Agents ◽  
Cytotoxic Activities ◽  
Hydroxybenzoic Acid ◽  
Derivatives Of

Two ether and one ester derivatives of the 4-nitro-3-hydroxybenzoic acid were synthesized and characterized. The in vitro antimicrobial and cytotoxic activities of the three novel compounds were also evaluated. The aromatic derivatives showed antibacterial activity against one of the four microorganisms tested and two compounds (C8 and NOBA) had a lower IC50 in HeLa cells.

scholarly journals In Vitro Cytotoxic Effects of Secondary Metabolites Present in Sarcopoterium Spinosum L.

2021 ◽  
Vol 11 (11) ◽  
pp. 5300
Author(s):  
Jozef Hudec ◽  
Jan Mojzis ◽  
Marta Habanova ◽  
Jorge A. Saraiva ◽  
Pavel Hradil ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Ethyl Acetate ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Benzalkonium Chloride ◽  
Ethanol Extract ◽  
Cytotoxic Activities ◽  
Sarcopoterium Spinosum ◽  
Mcf 7

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.

scholarly journals Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioiso-Mers for Antimalarial, Antiproliferative and Antimicrobial Activities

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3268
Author(s):  
Katja S. Håheim ◽  
Emil Lindbäck ◽  
Kah Ni Tan ◽  
Marte Albrigtsen ◽  
Ida T. Urdal Helgeland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antimicrobial Activities ◽  
Ring System ◽  
Human Prostate ◽  
The Novel ◽  
Human Prostate Cancer ◽  
Biofilm Inhibition

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).

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