scholarly journals Synthesis, Anticancer Activity, and Apoptosis Induction of Novel 3,6-Diazaphenothiazines

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 267 ◽  
Author(s):  
Beata Morak-Młodawska ◽  
Krystian Pluta ◽  
Małgorzata Latocha ◽  
Małgorzata Jeleń ◽  
Dariusz Kuśmierz
Keyword(s):  
Cell Lines ◽  
Triple Bond ◽  
Apoptosis Induction ◽  
Anticancer Activities ◽  
Expression Ratio ◽  
Qpcr Method ◽  
Amine Groups ◽  
C 32 ◽  
Derivatives Of ◽  
Mb231 Cell

New 10-substituted derivatives of 3,6-diazaphenothiazine, containing the triple bond linker terminated with tertiary cyclic and acyclic amine groups, were synthesized and screened for their anticancer action. The compounds exhibited varied anticancer activities against human glioblastoma SNB-19, melanoma C-32, and breast cancer MDA-MB231 cell lines, depending on the nature of the substituents. The most active 3,6-diazaphenothiazine, 4, was the derivative with the N,N-diethylamino-2-butynyl substituent against glioblastoma SNB-19, and was ten times more potent than cisplatin. For this compound, the expression of H3, TP53, CDKN1A, BCL-2, and BAX genes was detected by the RT-qPCR method. The gene expression ratio BAX/BCL-2 indicated the induction of mitochondrial apoptosis in cancer cell lines. The transformation of the propynyl substituent into amino-2-butynyl can be a method applicable to the search for more anticancer-active azaphenothiazines.

scholarly journals Design and Evaluation of Licochalcone A Derivatives as Anticancer Agents

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300
Author(s):  
Goo Yoon ◽  
Seung Hoon Cheon ◽  
Jung Hyun Shim ◽  
Seung Sik Cho
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Licochalcone A ◽  
Lead Compounds ◽  
Further Development ◽  
Derivatives Of

New derivatives of licochalcone A were synthesized and evaluated for their potential anticancer activities. Compounds 6 (( E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxy phenyl) acryloyl) phenyl)-4-isopropylbenzamide) and 8 (1-(3-dimethylamino-phenyl)-3-(2-trifluoromethyl-phenyl)-propenone) showed potent activity against the screened cancer cell lines with that of compound 6 ranging from 6.9 ± 0.2 μM to 22.9 ± 3.1 μM, and that of compound 8 from 4.2 ± 0.5 μM to 11.8 ± 0.7 μM. Both compounds showed stronger cytotoxicity than that of licochalcone A. These two candidates have very different substituents and could be considered as promising lead compounds for further development of potent anticancer agents.

scholarly journals Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 737
Author(s):  
Elwira Chrobak ◽  
Maria Jastrzębska ◽  
Ewa Bębenek ◽  
Monika Kadela-Tomanek ◽  
Krzysztof Marciniec ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Cell Lines ◽  
Human Cancer ◽  
Amelanotic Melanoma ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
C 32 ◽  
New Compounds ◽  
Derivatives Of

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.

Novel 1,3,4-Thiadiazole Linked Amide Derivatives of Pteridone: Synthesis and Study of Anticancer Activities

2019 ◽  
Vol 17 (1) ◽  
pp. 54-60
Author(s):  
Eeduri R. Devi ◽  
Reddymasu Sreenivasulu ◽  
Koya P. Rao ◽  
Ratnakaram V. Nadh ◽  
Malladi Sireesha
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Positive Control ◽  
Anticancer Activities ◽  
Human Cancer Cell Lines ◽  
Mtt Method ◽  
Amide Derivatives ◽  
Derivatives Of ◽  
A549 Lung ◽  
Mcf 7

Cancer is a second leading cause of death after heart attack, in developing as well as undeveloped countries. It is caused by unregulated growth and metastasis of the abnormal cancer cells. Cancer can be cured by radiation, immunotherapy and chemotherapy, among them; chemotherapy is a good treatment for cancer, in which chemotherapeutic drug is used. The anticancer activity of newly synthesized compounds (13a-j) was carried out on four different types of human cancer cell lines like MCF-7 (breast), A549 (lung), Colo-205 (colon) and A2780 (ovarian) by the MTT method, and compared to etoposide used as a positive control. Among them, compound 13g with electron-withdrawing (3,5-dinitro) group, exhibited more promising activity in all cell lines (MCF-7 = 0.10±0.076 µM, A549 = 0.17±0.039 µM, Colo-205= 0.13±0.022 µM and A2780 = 0.87±0.027µM). This compound may act as lead drug in cancer chemotherapy. In future, this compound can be examined for clinical studies.

Design, synthesis, anticancer activity and mechanism studies of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid

2022 ◽  
Author(s):  
Wen-Yan Wang ◽  
Zihui Yang ◽  
A-Liang Li ◽  
Qing-Song Liu ◽  
Yue Sun ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Ursolic Acid ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Pyrimidine Derivatives ◽  
Design Synthesis ◽  
Derivatives Of ◽  
Mcf 7

A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a...

Syntheses and Cytotoxicity Screening of some Novel 1,2,4-Triazine Derivatives against Liver Carcinoma Cell Lines

2020 ◽  
Vol 17 ◽  
Author(s):  
W. Abd El-Fattah
Keyword(s):  
Acetic Anhydride ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Aromatic Aldehydes ◽  
Liver Carcinoma ◽  
Anticancer Activities ◽  
Carcinoma Cell Lines ◽  
Elemental Analyses ◽  
Triazine Derivatives ◽  
C Nmr

: In this work, 1,2,4-triazine derivatives were synthesized and evaluated for anticancer activities. Series of 1,2,4-triazine derivatives (4a, b) were prepared via the reaction of N-benzoyl glycine (1) with aromatic aldehydes in presence of fused sodium acetate and acetic anhydride to give 1,3-oxazolinone derivatives (2a, b), followed by condensation with 1-(ethoxycarbonyl) hydrazine (3) in glacial acetic acid. Compounds (4a, b) then reacted with acetic anhydride, ethyl chloroacetate and 2,4-dinitrophenyl hydrazine yielded the corresponding to N-acetyl derivatives (5a, b), N-(ethoxycarbonyl) methyl derivative (6) and 1,2-disubstituted hydrazine (7), respectively. The structures of the 1,2,4-triazine derivatives were confirmed by IR, 1H, 13C NMR, MS and elemental analyses. Anticancer activity of some 1,2,4-triazine derivatives (4-7) have been investigated. The results revealed that compounds 4a (IC50= 2.7μM), 5a (IC50= 1.5μM), and 5b (IC50= 3.9μM) show promising inhibitory growth efficacy compared to a standard antitumor drug (IC50= 4.6μM). These three compounds can be considered as potential agents against human hepatocellular carcinoma cell lines (HepG-2).

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

2019 ◽  
Vol 15 (5) ◽  
pp. 550-560
Author(s):  
Mateusz D. Tomczyk ◽  
Anna Byczek-Wyrostek ◽  
Klaudia Strama ◽  
Martyna Wawszków ◽  
Przemysław Kasprzycki ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Topoisomerase Ii ◽  
Significant Activity ◽  
Anticancer Activities ◽  
Human Colon Cancer ◽  
Substitution Pattern ◽  
Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

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.

Synthesis and Cytotoxicity Assessment of Novel 7-O- and 14-O-Derivatives of Glaucocalyxin A

2020 ◽  
Vol 20 (10) ◽  
pp. 1241-1249
Author(s):  
Hong-Chuan Liu ◽  
Li-Ming Qiao ◽  
Wei Zheng ◽  
Zhao-Bao Xiang ◽  
Hai-Sheng Chen ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Folk Medicine ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Human Cancer Cell Lines ◽  
Derivatives Of

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure- Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study was to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds showed potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presented the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induced weak apoptosis of A549 cells but showed great potential in stimulating the apoptosis of HL- 60 cells. Acute toxicity assays indicated that compound 17 is relatively safer. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibited greater cytotoxicity against leukemia cells than against other types of tumors. In particular, 7,14-diacylation product of GLA was found to be an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme

2018 ◽  
Vol 18 (8) ◽  
pp. 1184-1196 ◽  
Author(s):  
Abdel-Ghany A. El-Helby ◽  
Helmy Sakr ◽  
Rezk R.A. Ayyad ◽  
Khaled El-Adl ◽  
Mamdouh M. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Kinase Assay ◽  
Anticancer Activities ◽  
In Silico Admet ◽  
Human Colon Adenocarcinoma ◽  
Mcf 7

Background: Extensive studies were reported in the synthesis of several phthalazine derivatives as promising anticancer agents as potent VEGFR-2 inhibitors. Vatalanib (PTK787) was the first anilinophthalazine published derivative as a potent inhibitor of VEGFR. The discovery of vatalanib as a clinical candidate led to the design and synthesis of different anilinophthalazine derivatives as potent inhibitors for VEGFR-2. The objective of present research work is the synthesis of new agents with the same essential pharmacophoric features of the reported and clinically used VEGFR-2 inhibitors (e.g vatalanib and sorafenib). The main core of our molecular design rationale comprised bioisosteric modification strategies of VEGFR-2 inhibitors at four different positions. </P><P> Material and Methods: A correlation between structure and biological activity of our designed phthalazines was established using molecular docking and VEGFR-2 kinase assay. Results and Discussion: In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0.06, 13±0.11, 15±0.14 and 23±0.22 µM respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer activities against MCF-7 breast cancer with IC50 of 16.98±0.15, 18.2±0.17, 57.54±0.53 and 66.45±0.67 µM respectively. Sorafenib as a highly potent VEGFR-2 inhibitor was used as a reference drug with IC50 of 5.47±0.3 and 7.26±0.3 µM respectively. Nine compounds were further evaluated for their VEGFR-2 inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active counterparts against VEGFR-2 with IC50 values of 0.1±0.01, 0.15±0.02, 0.28±0.03 and 0.38±0.04 µM, respectively comparable to that of sorafenib (IC50 = 0.1±0.02) µM. Furthermore, molecular docking studies were carried out for all synthesized compounds to investigate their binding pattern and predict their binding affinities towards VEGFR-2 active site. In silico ADMET studies were calculated for the tested compounds. Most of our designed compounds exhibited good ADMET profile. Conclusion: The obtained results showed that, the most active compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs.

scholarly journals Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4288
Author(s):  
Fernanda Malhão ◽  
Ana Catarina Macedo ◽  
Carla Costa ◽  
Eduardo Rocha ◽  
Alice Abreu Ramos
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
3D Models ◽  
Anticancer Activities ◽  
Cytotoxic Effects ◽  
3D Cultures ◽  
3D Cell Cultures ◽  
Tumoral Cell ◽  
Microscopy Techniques ◽  
2D And 3D

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

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