scholarly journals New Chitosan Polymer Scaffold Schiff Bases as Potential Cytotoxic Activity: Synthesis, Molecular Docking, and Physiochemical Characterization

2022 ◽  
Vol 9 ◽  
Ponnusamy Packialakshmi ◽  
Perumal Gobinath ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
Raman Gurusamy ◽  

In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (1H—13C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI50 value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC50 > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an in-silico study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (−5.9 kcal/mol) and a lower binding affinity for Doxorubicin (−5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.

2018 ◽  
Vol 18 (4) ◽  
pp. 573-582 ◽  
Khaled R.A. Abdellatif ◽  
Mostafa M. Elbadawi ◽  
Mohammed T. Elsaady ◽  
Amer A. Abd El-Hafeez ◽  
Takashi Fujimura ◽  

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2212
Mohammad Shahidul Islam ◽  
M. Ali ◽  
Abdullah Mohammed Al-Majid ◽  
Abdullah Saleh Alamary ◽  
Saeed Alshahrani ◽  

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC50 values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC50 = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC50 = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC50 = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  

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.

2018 ◽  
Vol 11 (3) ◽  
pp. 204-208
Ivana Šušaníková ◽  
Adriána Kvasnicová ◽  
Žofia Brzková ◽  
Ondrej Ďuriška ◽  
Pavel Mučaji

Abstract The aim of the research was to determine some basic biological activities of less biomedically studied but commonly known two fungi from the Boletaceae family Suillellus rubrosanguineus and Tylopilus felleus, which grow in the forests of Middle Europe. The cytotoxicity tests of the ethanol and chloroform extracts were carried out using NIH-3T3 and MCF-7 cell lines. The presence of alkaloids in the extracts was assessed by the reaction with Dragendorff reagent. In all of the extracts the positive reaction with the reagent was observed. In general, the extracts from Suillellus rubrosanguineus were more cytotoxic than the extracts from Tylopilus felleus and exhibited no selectivity of activities on healthy and cancer cell lines. However, the extracts from Tylopilus felleus proved to be selectively cytotoxic for cancer cell line. Tylopilus extracts or their isolated bioactive compounds could be considered for further study in pre-clinical experiments.

Jie Wu ◽  
Li Zhang ◽  
Qian Song ◽  
Lei Yu ◽  
Shuyuan Wang ◽  

Abstract The CCCTC-binding factor (CTCF) mediates transcriptional regulation and implicates epigenetic modifications in cancers. However, the systematically unveiling inverse regulatory relationship between CTCF and epigenetic modifications still remains unclear, especially the mechanism by which histone modification mediates CTCF binding. Here, we developed a systematic approach to investigate how epigenetic changes affect CTCF binding. Through integration analysis of CTCF binding in 30 cell lines, we concluded that CTCF generally binds with higher intensity in normal cell lines than that in cancers, and higher intensity in genome regions closed to transcription start sites. To facilitate the better understanding of their associations, we constructed linear mixed-effect models to analyze the effects of the epigenetic modifications on CTCF binding in four cancer cell lines and six normal cell lines, and identified seven epigenetic modifications as potential epigenetic patterns that influence CTCF binding intensity in promoter regions and six epigenetic modifications in enhancer regions. Further analysis of the effects in different locations revealed that the epigenetic regulation of CTCF binding was location-specific and cancer cell line-specific. Moreover, H3K4me2 and H3K9ac showed the potential association with immune regulation of disease. Taken together, our method can contribute to improve the understanding of the epigenetic regulation of CTCF binding and provide potential therapeutic targets for treating tumors associated with CTCF.

2021 ◽  
Maged Mostafa Mahmoud ◽  
Ahmed M. Al-Hejin ◽  
Turki S. Abujamel ◽  
Modhi Alenezi ◽  
Fadwa Aljoud ◽  

Abstract This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. It was found during the study that exposure of cell lines to higher concentration of chicken cathelicidin for 72 h reduced cell lines growth rate by 90%-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) which are essential for G1/S phase transient and S/G2 phase and consequently causes “prometaphase arrest” ultimately leading to death of MCF-7 cells. The study showed two- and three-times higher expression of the caspase-3, and − 7 genes respectively in MCF-7 cells treated with chicken peptides (especially cathelicidin-2 and − 3) relative to untreated cells which encouraged pro-apoptotic pathway, autophagy, and augmentation of the anti-proliferative activity. Our data showed that chicken ( CATH-1 ) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups after cathelicidin administration compared to untreated EAC-bearing group. Additionally, animals received high dose of cathelicidin-1 (40 µg/ml) displayed an apical survival rate compared to untreated carcinoma control and animals which received low dose of cathelicidin (10 and 20 µg/ml). Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg/ml of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/ml of CATH-1. This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 830
Mookho S. Lerata ◽  
Sarah D’Souza ◽  
Nicole R.S. Sibuyi ◽  
Admire Dube ◽  
Mervin Meyer ◽  

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 μM vs. 8.94 μM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 μM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 μM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

Folia Medica ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 104-112 ◽  
Kaloyan D. Georgiev ◽  
Iliya J. Slavov ◽  
Ivan A. Iliev

Abstract Background: Lycium barbarum has gained immense popularity over the past decade because of its antioxidant properties. There are many reports of observed health benefits of juice consumption, including prophylaxis in neoplastic disease and treatment of tumors. Materials and methods: In this study, we isolated three fractions of Lycium barbarum fruits – total water, pectin-free and polysaccharide, and determined their antioxidant activity by ORAC and HORAC assays. We investigated the antiproliferative effects of Lycium barbarum’s pectin-free and polysaccharide fraction on three different breast cell lines - MCF-10A (non-tumorigenic epithelial breast cell line), MCF-7 (breast cancer cell line, estrogen, progesterone receptors +, HER2-), and MDA-MB-231 (breast cancer cell line, triple negative), by the MTT dye reduction assay. Results: The Lycium barbarum’s pectin-free fraction showed concentration-dependent growth inhibition on the three cell lines, moreover, on cancer cells (MCF- 7 and MDA-MB-231) it was significantly more pronounced. The polysaccharide fraction showed negligible activity on the three cell lines, only the highest concentration (1000 μg/mL), suppressed the proliferation of MCF-7 cells. The combination of pectin-free and polysaccharide fraction on MCF-7 did not show the expected synergistic effect. Conclusion: We found a relative correlation between the polyphenolic content of the extracts and the observed effects. The pectin-free extract had the highest content of polyphenols with the best antioxidant and antineoplastic activity against breast cancer cells. Addition of polysaccharide to the pectin-free fraction contributes to its pharmacological activity.

2012 ◽  
Vol 2 (6) ◽  
pp. 242 ◽  
Hong-Hong Zhu ◽  
Guo-Hui Huang ◽  
Patricia L. Tate ◽  
Lyndon L. Larcom

Objective: Danggui, the root of Angelica Sinensis, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism. Methods: Danggui was extracted by ethanol. The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368) and cervical (CaSki and SiHa) cancer cells with its effects on normal fibroblasts (HTB-125). A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonella typhimarium (TA) 100 and 102 were used in the test. Methyl methane sulfonate (MMS) and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW) as controls. The SAS statistical software was used to analyze the data. Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID50) of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, respectively. For the normal fibroblasts, ID50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3 % of the normal HTB-125 cells were killed. Revertants per plate of TA 100 decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as a mutagen. There was no difference in revertants per plate between ethanol and DDW control groups. Conclusions: Danggui could be used as a safe and effective adjuvant therapy to prevent and treat breast and cervical cancers. Anti-cancer effects may be due to its anti-mutagenicity. Danggui should be investigated as a potential adjuvant anti-cancer therapy for women’s cancer treatment and prevention of recurrence. Key words: Angelica Sinensis, Danggui, cancer, women’s reproductive disorders

Fatemeh Hajipour ◽  
Masoud Mahdavinia ◽  
Masood Fereidoonnezhad

Background and Objective: In the design of modern metal-based anticancer drugs, platinum-based complexes have gained growing interest. In this study, the anticancer activity of half-lantern cyclometalated Pt(II)‒Pt(II) complexes were was evaluated using MTT, apoptosis, cell cycle analysis, and DNA binding studies. Materials and Methods: The cytotoxicity of Pt(II)‒Pt(II) complexes were evaluated against different cancer cell lines such as human lung (A549), breast (MCF-7, and MDA-MB-231), ovarian (SKOV-3), and colon (HT-29) as well as normal breast (MCF-10A), and human lung fibroblast MRC-5 cells using MTT assay. BioLegend's PE Annexin V Apoptosis Detection Kit with 7AAD was applied to assess the apoptotic effects of 1A, and 1B compound against MCF-7, and A549 cell lines. Cell cycle analysis was determined using the flowcytometry method. The interaction of compounds with four different DNA structures with PDB codes (1BNA, 1LU5, 3CO3, and 198D) has been investigated by molecular docking. To achieve binding to DNA experimentally, the electrophoresis mobility shift assay and comet assay was applied. Results: In the evaluation of cytotoxic effects, 1A showed the highest cytotoxicity among the studied compounds, and it showed higher potency with more selectivity against normal cell lines than cisplatin. This compound had IC50 of 7.24, 2.21, 1.18, 2.71, 10.65, 18.32 and 49.21 μM against A549, SKOV3, HT29, MCF-7, MDA-MB-231, MRC-5, and MCF-10A, respectively, whereas cisplatin had IC50 of 9.75, 19.02, 107.23, 15.20, 18.09, 14.36, and 24.21 μm, respectively, on the same cell lines. In order to check the DNA binding activity of 1A, and 1B, electrophoretic mobility was also conducted, which indicated that the binding of these compounds led to a slight change in electrophoretic mobility to DNA. The migration of chromosomal DNA from the nucleus in the form of a tail or comet was executed in the comet assay of 1A on MCF-7. Examination of apoptosis of 1A, and 1B on the MCF-7 cancer cell line, showed that it could increase induction of apoptosis in this cancerous cell in a concentration-dependent manner. Investigating the effect of 1A using cell cycle analysis on MCF-7 cancer cell line showed that this complex affects the stage G1 and S of the cell cycle. Conclusion: 1A has the potential to play a significant role in future biopharmaceutical studies.

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