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 Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 192 ◽  
Author(s):  
Urszula Majcher ◽  
Greta Klejborowska ◽  
Mahshad Moshari ◽  
Ewa Maj ◽  
Joanna Wietrzyk ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Binding Modes ◽  
Long Term Treatment ◽  
Colchicine Derivatives ◽  
Β Tubulin ◽  
Mcf 7

Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.

scholarly journals Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

2021 ◽  
Author(s):  
ulviye acar çevik ◽  
Ismail Celik ◽  
Ayşen IŞIK ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Evaluation Studies ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Anticancer Activities ◽  
Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines

2019 ◽  
Vol 16 (2) ◽  
pp. 294-302 ◽  
Author(s):  
Hui Gao ◽  
Bei Liu ◽  
Ping Zhu ◽  
Li-Jun Zhang ◽  
Chun-Ping Wan ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Human Tumor ◽  
Biological Evaluation ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Aim and Objective: Isoxazolines are an important class of nitrogen and oxygen-containing heterocycles, which have gained much importance as the potential biological agents. In order to study structureactivity relationships of isoxazolines, this work has been conducted. Materials and Methods: A series of new piperazine substituted 3, 5-diarylisoxazoline derivatives (6-31) were designed and synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anticancer effect against a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated. Results: The substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 5, 7, 8, 10, 11, 13 and 27-showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, derivatives 5, 6, 7, 8, 9, 13 and 26 were found to be potential selectively anticancer activity on human tumor cell lines, which displayed better cytotoxic activity to positive control 5- FU. Conclusion: Piperazine substituted 3, 5-diarylisoxazoline derivatives could be considered as new antiinflammatory and anticancer agents.

Design, Synthesis of novel coumarin conjugated acetamides as promising anticancer agents: An in-silico and in-vitro approach.

2020 ◽  
Vol 20 ◽  
Author(s):  
Mamatha S. V ◽  
S. L. Belagali ◽  
Mahesh Bhat ◽  
Vijay M. Kumbar
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Mtt Assay ◽  
Anticancer Agents ◽  
In Silico ◽  
Active Sites ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Mcf 7

Background: Coumarin and benzophenone possess a vast sphere of biological activities whereas thiazoles display various pharmacological properties. Hence we focused on incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity anticipating their interesting biological properties. Objective: The objective of the current work is synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. Methods: A novel series of Coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by multistep reaction sequence and were characterized by the FT-IR, LCMS and NMR spectral techniques. The newly synthesized compounds were screened for anticancer activity by in-silico and in-vitro methods. The cytotoxicity of the synthesized unique compounds had been executed for two different cancer cell lines MCF-7 (Breast cancer) and KB (Oral cancer) in comparison with standard paclitaxel by MTT assay. Results: The compound 7f is the potent motif with an acceptable range of IC 50 values for anticancer activity were 63.54 µg/ml and 55.67 µg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids MET 769, ARG 817 and LYS 721. Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

scholarly journals Biological Evaluation of 3-Aminoisoquinolin-1(2H)-one Derivatives as Potential Anticancer Agents Authors Lyudmyla Potikha

2021 ◽  
Vol 9 (2) ◽  
pp. 52-63
Author(s):  
Lyudmyla Potikha ◽  
◽  
Volodymyr Brovarets ◽  
Victor Zhirnov ◽  
◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Tumor ◽  
Biological Evaluation ◽  
Tumor Cell Growth ◽  
Epithelial Cancer ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Anticancer activity of a series of 3-(hetaryl/aryl)amino substituted isoquinolin-1(2H)-ones has been studied within the international scientific program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with thiazolyl or pyrazolyl substituent at 3-amino group and had no substituents at C(4) of the isoquinoline cycle. We identified a new lead compound, 3-(1,3-thiazol-2-ylamino)isoquinolin-1(2H)-one 12, which effectively prevents tumor cell growth (average lg GI50 = -5.18, lg TGI = -4.1, lg LC50 > -4.0) with good selectivity.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

In Vitro Evaluation of Chitosan Induced Cytotoxicity against Cancerous Cell lines: MCF-7, Saos-2 and HeLa

2019 ◽  
Vol 19 ◽  
Author(s):  
Zeinab Abedian ◽  
Niloofar Jenabian ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Roghayeh Pourbagher ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Fibroblast Cells ◽  
Apoptosis Induction ◽  
Cytotoxic Effects ◽  
Cancerous Cell ◽  
Significant Concentration ◽  
Mcf 7

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

scholarly journals Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Design And Synthesis ◽  
Human Breast Cell ◽  
Mcf 7

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1789 ◽  
Author(s):  
Julia Krzywik ◽  
Witold Mozga ◽  
Maral Aminpour ◽  
Jan Janczak ◽  
Ewa Maj ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Docking Studies ◽  
Binding Modes ◽  
Colchicine Binding Site ◽  
3T3 Cell Lines ◽  
Colchicine Derivatives

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 10 ◽  
Author(s):  
Hehua Xiong ◽  
Jianxin Cheng ◽  
Jianqing Zhang ◽  
Qian Zhang ◽  
Zhen Xiao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Docking Simulation ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

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