scholarly journals Bifunctional Phenol Quinone Methide Precursors: Synthesis and Biological Activity

2019 ◽  
Vol 92 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Matija Sambol ◽  
Katja Ester ◽  
Antonija Husak ◽  
Đani Škalamera ◽  
Ivo Piantanida ◽  
...  
Keyword(s):  
Biological Activity ◽  
Rational Design ◽  
Human Cancer ◽  
Conclusive Evidence ◽  
Biologically Active ◽  
Quinone Methide ◽  
Breast Adenocarcinoma ◽  
Cross Link ◽  
Human Cancer Cell Lines ◽  
Sequential Generation

New bifunctional quinone methide (QM) precursors, bisphenols 2a–2e, and monofunctional QM precursor 7 were synthesized. Upon treatment with fluoride, desilylation triggers formation of reactive intermediates, QMs, which was demonstrated by trapping QM with azide or methanol. The ability of QMs to alkylate and cross-link DNA was assayed by investigation of the effects of QMs to DNA denaturing, but without conclusive evidence. Furthermore, treatment of a plasmid DNA with compounds 2a–2e and KF, followed by the analysis by alkaline denaturing gel electrophoresis, did not provide evidence for the DNA cross-linking. MTT test performed on two human cancer cell lines (MCF7 breast adenocarcinoma and SUM159 pleomorphic breast carcinoma), with and without fluoride, indicated that 2a–2e or the corresponding QMs did not exhibit cytotoxic activity, in line with the lack of ability to cross-link DNA. The lack of reactivity with DNA and biological activity were explained by sequential formation of QMs where bifunctional cytotoxic reagent is probably never produced. Instead, the sequential generation of monofunctional QM followed by a faster hydrolysis leads to the destruction of biologically active reagent. The findings described here are particularly important for the rational design of new generation of QM precursor molecules that will attain desirable DNA reactivity and cytotoxicity.

scholarly journals Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3355
Author(s):  
Matija Sambol ◽  
Patricia Benčić ◽  
Antonija Erben ◽  
Marija Matković ◽  
Branka Mihaljević ◽  
...  
Keyword(s):  
Biological Activity ◽  
Rational Design ◽  
Human Cancer ◽  
Photophysical Properties ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Quinone Methide ◽  
Quantum Yields ◽  
Photochemical Reactivity ◽  
Human Cancer Cell Lines

Quinone methide precursors 1a–e, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (ΦF ≈ 10−2). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (ΦR ≈ 10−5). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that 1a and 1e form complexes with ct-DNA with moderate association constants Ka ≈ 105–106 M−1, as well as with bovine serum albumin (BSA) Ka ≈ 105 M−1 (1:1 complex). The irradiation of the complex 1e@BSA resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of 1a–e against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for 1e (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light.

Novel 1,2,3-Triazole-functionalized pyrido[3',2':4,5]furo[3,2-d]pyrimidin- 4(3H)-one Derivatives: Synthesis, Anticancer Activity, CoMFA and CoMSIA Studies

2020 ◽  
Vol 17 (12) ◽  
pp. 969-978
Author(s):  
Balakishan Vadla ◽  
Sailu Betala
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Normal Cell ◽  
Rational Design ◽  
Human Cancer ◽  
Strong Basis ◽  
Hek 293 ◽  
Normal Cell Line ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido [3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer (CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.

Glyoxyl analogs of indole phytoalexins: Synthesis and anticancer activity

2010 ◽  
Vol 75 (8) ◽  
pp. 887-903 ◽  
Author(s):  
Peter Kutschy ◽  
Andrej Sýkora ◽  
Zuzana Čurillová ◽  
Mária Repovská ◽  
Martina Pilátová ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Line ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Breast Adenocarcinoma ◽  
Human Cancer Cell Lines ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Indole Phytoalexins

Glyoxyl analogs of indole phytoalexins brassinin, 1-methoxybrassinin, brassitin, 1-methoxybrassitin and 1-methoxybrassenin B were prepared, using (1H-indol-3-yl)-, (1-methoxyindol-3-yl)- and [1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl]glyoxyl chlorides as starting compounds. Synthesized products were examined for their antiproliferative activity against human cancer cell lines Jurkat (T-cell acute lymphoblastic leukemia), MCF-7 (breast adenocarcinoma, estrogen receptor-positive), MDA-MB-231 (breast adenocarcinoma, estrogen receptor-negative), HeLa (cervical adenocarcinoma), CCRF-CEM cell line (T-cell acute lymphoblastic leukemia) and A-549 cell line (lung adenocarcinoma), and their activity compared with natural phytoalexins and corresponding (1H-indol-3-yl)acetic acid derivatives. The highest potency with IC50 3.3–66.1 μmol l–1 was found for glyoxyl analogs of 1-methoxybrassenin B.

CYTOTOXIC ACTIVITY OF LUVUNGA SCANDENS AGAINST HUMAN CANCER CELL LINES

2016 ◽  
Vol 78 (10) ◽  
Author(s):  
Putri Nur Hidayah Al-Zikri ◽  
Muhammad Taher ◽  
Deny Susanti ◽  
Solachuddin Jauhari Arief Ichwan
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
A549 Cell ◽  
Human Cancer ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Human Cancer Cell Lines ◽  
Mcf 7

Luvunga scandens belongs to the family of Rutaceae which usually inhabit tropical and moist environment. This plant is known as ‘Mengkurat Jakun’ among locals and used traditionally to treat fever and fatigue via decoction. The aim of this study was to investigate the cytotoxic activity of the leaves and stems extracts of L. scandens extract. Extracts of the leaves and stems were obtained from sequential extraction procedures by various organic solvents. All extracts were subjected to cytotoxic study by 3-(4, 5-dimethylthaizol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. In in vitro cytotoxicity assay, all L. scandens extracts exhibited cytotoxicity against human breast adenocarcinoma (MCF-7) and human lung adenocarcinoma (A549) cell lines. The IC50 values of dichloromethane and methanol extracts from the leaves of L. scandens against MCF-7 cell line were 62.5 µg/mL and 88.0 µg/mL, respectively, whereas IC50 of methanol extract from stem was 81.0 µg/mL. All extracts were less active against A549 cell line where IC50 value were not be determined. The present findings revealed the potential of L. scandens as a cytotoxic agent against MCF-7 cell line. However, further studies should be planned to evaluate role of the plant in cytotoxic activity.

scholarly journals Synthesis of Novel Class of N-Alkyl-isatin-3-iminobenzoic Acid Derivatives and Their Biological Activity in Zebrafish Embryos and Human Cancer Cell Lines

2018 ◽  
Vol 41 (3) ◽  
pp. 350-359 ◽  
Author(s):  
Muhammad Farooq ◽  
Zainab Mohammed Al Marhoon ◽  
Nael Abu Taha ◽  
Almohannad Abdulrahman Baabbad ◽  
Mohammed Ahmed Al-Wadaan ◽  
...  
Keyword(s):  
Biological Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Zebrafish Embryos ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

scholarly journals Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4860
Author(s):  
Ladislav Janovec ◽  
Eva Kovacova ◽  
Martina Semelakova ◽  
Monika Kvakova ◽  
Daniel Kupka ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Biologically Active ◽  
Standard Entropy ◽  
The Novel ◽  
Urea Derivatives ◽  
Human Cancer Cell Lines ◽  
Pharmacological Model

A novel series of proflavine ureas, derivatives 11a–11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b–0.44 μM, phenyl 11c–0.23 μM, phenylethyl 11f–0.35 μM and hexyl 11j–0.36 μM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.

scholarly journals Thermal behavior and biological activity of [Co2(Cl)2 tpmc](BF4)2 complex

2021 ◽  
Vol 62 (4) ◽  
pp. 291-296
Author(s):  
Slađana Tanasković ◽  
Mirjana Antonijević-Nikolić ◽  
Branka Dražić
Keyword(s):  
Biological Activity ◽  
Human Cancer ◽  
Chair Conformation ◽  
Single Step ◽  
Moderate Activity ◽  
Human Cancer Cell Lines ◽  
Highly Active ◽  
Dta Analysis

A large number of interesting Co (II) complexes with macrocyclicligands have been synthesized and the recognition of its complexes as important bioactive compounds in vitro and in vivo has aroused growing interest in these agents as potential drugs for therapeutic use in various diseases. Numerous available information on their bioinorganic properties and mode of action in several biological systems, combined with the new possibilities imposed by the development of medical chemistry, opens space for the development of a new generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to present some properties of the earlier isolated the first Co(II)tpmc complex for which crystal structure confirmed chair conformation of macrocycle. Complex with formula (Co2(Cl)2tpmc)(BF4)2 (tpmc = N,N`,N``,N```tetrakis(2-pyridylmethyl)-1,4,8,11 - tetraazacyclotetradecane), was studied on thermal behaviour and biological activity. TG-DTA analysis indicates that complex decomposition in a single step in the range of 365 -435 °C. Investigated cytotoxic activity against two human cancer cell lines: HeLa (human cervix adenocarcinoma) and K562 (human myelogenous leukaemia). Complex was also preliminary assayed in vitro toward bacteria, fungi and mould together with the starting material for the synthesis (ligands, simple salts and solvents) as test substances. Investigated complex showed a moderate activity against strains of bacteria and were inactive against the tested fungi and mould. Minimal inhibitory concentration suppressing the visible growth of bacteria was determined. Biological investigations show the complex has significant cytotoxic potential.

scholarly journals Copper(II) Complexes Containing Natural Flavonoid Pomiferin Show Considerable in Vitro Cytotoxicity and Anti-Inflammatory Effects

2021 ◽  
Vol 22 (14) ◽  
pp. 7626
Author(s):  
Ján Vančo ◽  
Zdeněk Trávníček ◽  
Jan Hošek ◽  
Tomáš Malina ◽  
Zdeněk Dvořák
Keyword(s):  
Ovarian Carcinoma ◽  
Human Cancer ◽  
Annexin V ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Monocytic Leukemia ◽  
Healthy Human ◽  
Human Cancer Cell Lines ◽  
Anti Inflammatory

A series of new heteroleptic copper(II) complexes of the composition [Cu(L)(bpy)]NO3·2MeOH (1), [Cu(L)(dimebpy)]NO3·2H2O (2), [Cu(L)(phen)]NO3·2MeOH (3), [Cu(L)(bphen)]NO3·MeOH (4), [Cu(L)(dppz)]NO3·MeOH (5) was prepared, where HL = 3-(3,4-dihydroxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-ene-1-yl)-4H,8H-benzo[1,2-b:3,4-b']dipyran-4-one, (pomiferin) and bpy = 2,2'-bipyridine, dimebpy = 4,4ʹ-dimethyl-2,2ʹ-bipyridine, phen = 1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, and dppz = dipyrido[3,2-a:2',3'-c]phenazine. The complexes were characterized using elemental analysis, infrared and UV/Vis spectroscopies, mass spectrometry, thermal analysis and conductivity measurements. The in vitro cytotoxicity, screened against eight human cancer cell lines (breast adenocarcinoma (MCF-7), osteosarcoma (HOS), lung adenocarcinoma (A549), prostate adenocarcinoma (PC-3), ovarian carcinoma (A2780), cisplatin-resistant ovarian carcinoma (A2780R), colorectal adenocarcinoma (Caco-2) and monocytic leukemia (THP-1), revealed the complexes as effective antiproliferative agents, with the IC50 values of 2.2–13.0 μM for the best performing complexes 3 and 5. All the complexes 1–5 showed the best activity against the A2780R cells (IC50 = 2.2–6.6 μM), and moreover, the complexes demonstrated relatively low toxicity on healthy human hepatocytes, with IC50 > 100 μM. The complexes were evaluated by the Annexin V/propidium iodide apoptosis assay, induction of cell cycle modifications in A2780 cells, production of reactive oxygen species (ROS), perturbation of mitochondrial membrane potential, inhibition of apoptosis and inflammation-related signaling pathways (NF-κB/AP-1 activity, NF-κB translocation, TNF-α secretion), and tested for nuclease mimicking activity. The obtained results revealed the corresponding complexes to be effective antiproliferative and anti-inflammatory agents.

scholarly journals Synthesis and Anticancer Evaluations of Novel Thiazole Derivatives Derived from 4-Phenylthiazol-2-amine

2021 ◽  
Vol 68 (3) ◽  
pp. 604-616
Author(s):  
Amira E. M. Abdallah ◽  
Rafat M. Mohareb ◽  
Maher H. E. Helal ◽  
Germeen J. Mofeed
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Human Cell Line ◽  
Breast Adenocarcinoma ◽  
Small Cell Lung ◽  
Thiazole Derivatives ◽  
Human Cancer Cell Lines ◽  
Chemical Reagents ◽  
Cns Cancer ◽  
Mcf 7

Many novel thiazole derivatives were designed and synthesized using 4-phenylthiazol-2-amine. The reactivity of the latter compound toward different chemical reagents was studied. The structure of the newly synthesized compounds was established based on elemental analysis and spectral data. Furthermore, twenty compounds of the synthesized systems were selected and evaluated in (μM) as significant anticancer agents towards three human cancer cell lines [MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer)] and normal fibroblasts human cell line (WI-38). The results showed that compounds 9 and 14a displayed higher effeciency than the reference doxorubicin.

scholarly journals Cytotoxic Activity of Two Cembranoid Diterpenes from Nicotiana Sylvestris Against Three Human Cancer Cell Lines

2017 ◽  
Vol 5 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Amir Reza Jassbi ◽  
Marzieh Vafapour ◽  
Ardeshir Shokrollahi ◽  
Omidreza Firuzi ◽  
Mehdi Zare ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Nicotiana Sylvestris ◽  
Cancer Cell Lines ◽  
Breast Adenocarcinoma ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines

Background: Two cembranoid diterpenes, [(1S, 2E, 4R, 6R, 7E, 11E)-2, 7, 11-cembratriene-4, 6-diol] (1) and its epimer [(1S, 2E, 4S, 6R,7E,11E)-2, 7, 11-cembratriene-4, 6-diol] (2) were isolated from surface dichloromethane washings and chloroform extract of Nicotiana sylvestris leaves. Methods: The compounds were purified using silica gel column- thin layer- and flash column chromatography methods. The structures of the isolated compounds were elucidated using spectroscopic analysis and their 1H and 13C NMR spectroscopic data were compared with those of authentic samples reported in the literature. The cytotoxic activity of 1 and 2 against three human cancer cell lines, including LS180 (human colon adenocarcinoma), MCF-7 (human breast adenocarcinoma) and MOLT-4 (human lymphoblastic leukemia) were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric bioassay. Results: The IC50 values of compounds 1 and 2 were calculated to be between (28.4±3.7 up to 44.0±6.4 µM) (mean±S.E.M.) for the above mentioned cell lines.

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