Structural Modification of Sylibin to Derivatives of Sylibin/Hydnocarpin D /Silandrin, and Evaluation of Their Cytotoxicity Against Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Liwaliding Maihesuti ◽  
Hongwei Gao ◽  
Qi Wang ◽  
Jianguo Cao ◽  
Haji Akber Aisa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cancer Cells ◽  
Chemical Conversion ◽  
Molecular Iodine ◽  
Inhibitory Effect ◽  
Mtt Method ◽  
Amide Derivatives ◽  
Anti Cancer ◽  
Related Proteins ◽  
Derivatives Of

Background: Flavonolignans like silybin, hydnocarpin, and siliandrin are a group of natural compounds combining the structural moieties of flavonoid and phenylpropanoid (lignan). Hydnocarpin and silandrin were less explored because of trace occurrence in nature. Objective: The present study aimed to develop a chemical conversion of silybin to hydnocarpin, and siliandrin. Also, a series of amide derivatives would be synthesized and biologically evaluated with regard to their anti-cancer effects. Methods: In order to selectively convert silybin to 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin, the ratio of Ph3P, imidazole and molecular iodine was meticulously adjusted. These three iodide compounds were converted into amide compounds by chemical transformation. MTT method was applied to evaluate their anti-cancer potency. The binding affinity to related proteins was calculated by molecular docking. Results: Totally, 45 new amido-derivatives were synthesized and structurally characterized by NMR and HRMS. Some of them showed moderate to good antiproliferative potency against cancer cells. The activity of compound 10j was further testified by colony formation assay and molecular docking. Conclusion: Synthesis of 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin from silybin was successfully accomplished by one simple iodination reaction. Some of the amide derivatives of sylibin/hydnocarpin D /silandrin exhibit a remarkable inhibitory effect of proliferation on cancer cells as compared to silybin. These results would pave the way for further investigation on the derivatives of flavonolignans for the treatment of cancer.

Theoretical Study of the Process of Passage of Glycoside Amides through the Cell Membrane of Cancer Cell

2020 ◽  
Vol 20 ◽  
Author(s):  
Vasil Tsanov ◽  
Hristo Tsanov
Keyword(s):  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Quantum Chemical ◽  
Density Functional ◽  
Enzyme Regulation ◽  
Amide Derivatives ◽  
Pass Through ◽  
Hydrolysis Of ◽  
Derivatives Of

Background:: This article concentrates on the processes occurring in the medium around the cancer cell and the transfer of glycoside amides through their cell membrane. They are obtained by modification of natural glycoside-nitriles (cyano-glycosides). Hydrolysis of starting materials in the blood medium and associated volume around physiologically active healthy and cancer cells, based on quantum-chemical semi-empirical methods, is considered. Objective:: Based on the fact that the cancer cell feeds primarily on carbohydrates, it is likely that organisms have adapted to take food containing nitrile glycosides and / or modified forms to counteract "external" bioactive activity. Cancers, for their part, have evolved to create conditions around their cells that eliminate their active apoptotic forms. This is far more appropriate for them than changing their entire enzyme regulation to counteract it. In this way, it protects itself and the gene sets and develops according to its instructions. Methods:: Derived pedestal that closely defines the processes of hydrolysis in the blood, the transfer of a specific molecular hydrolytic form to the cancer cell membrane and with the help of time-dependent density-functional quantum- chemical methods, its passage and the processes of re-hydrolysis within the cell itself, to forms causing chemical apoptosis of the cell - independent of its non-genetic set, which seeks to counteract the process. Results:: Used in oncology it could turn a cancer from a lethal to a chronic disease (such as diabetes). The causative agent and conditions for the development of the disease are not eliminated, but the amount of cancer cells could be kept low for a long time (even a lifetime). Conclusion:: The amide derivatives of nitrile glycosides exhibit anti-cancer activity, the cancer cell probably seeks to displace hydrolysis of these derivatives in a direction that would not pass through its cell membrane and the amide- carboxyl derivatives of nitrile glycosides could deliver extremely toxic compounds within the cancer cell itself and thus block and / or permanently damage its normal physiology.

Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Shahram Taeb ◽  
Hamed Haghi-Aminjan ◽  
Shima Afrashi ◽  
Kave Moloudi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Fas Ligand ◽  
Inhibitory Effect ◽  
Mitochondrial Pathway ◽  
Multi Drug Resistance ◽  
Chemotherapy Drugs ◽  
Normal Tissues ◽  
Anti Cancer

: Resistance of cancer cells to therapy is a challenge for achieving an appropriate therapeutic outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to toxic agents such as chemotherapy drugs, radiation as well as immunotherapy. Evidences show that apoptosis plays a key role in response of cancer (stem) cells and their multi drug resistance. Modulation of both intrinsic and extrinsic pathways of apoptosis can increase efficiency of tumor response and amplify the therapeutic effect of radiotherapy, chemotherapy, targeted therapy and also immunotherapy. To date, several agents as adjuvant have been proposed to overcome resistance of cancer cells to apoptosis. Natural products are interesting because of low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown interesting anti-cancer properties. It has been shown to kill cancer cells selectively, while protecting normal cells. Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the expression of apoptosis receptors such as Fas ligand (FasL). Resveratrol also triggers some pathways which induce mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on anti-apoptotic mediators such as nuclear factor κ B (NFκB), cyclooxygenase-2 (COX-2), phosphatidylinositol 3–kinase (PI3K) and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.

Metformin Treatment Sensitizes Human Laryngeal Cancer Cell Line Hep- 2 to 5-Fluorouracil

2020 ◽  
Vol 7 (1) ◽  
pp. 16-24
Author(s):  
Neslisah Barlak ◽  
Fatma Sanli ◽  
Ozel Capik ◽  
Elanur Tuysuz ◽  
Elanur Aydın Karatas ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
Soft Agar ◽  
Invasive Potential ◽  
Matrigel Invasion ◽  
Soft Agar Assay ◽  
Anti Cancer ◽  
Apoptosis Assay ◽  
Cancer Types

Background: Larynx cancer (LCa) is the most common head and neck cancer and accounts for 1-2.5% of all human cancers worldwide. Metformin, an oral anti-diabetic drug, has been recently shown to have anti-cancer activity in various cancer types, and there are several studies in the literature pointing to its potential to sensitize cancer cells to chemotherapeutic drugs. Objective: This study was aimed at exploring the anti-cancer effects of metformin alone or in combination with 5-fluorouracil (5-FU) on Hep-2 cells. Methods: The effects of metformin and/or 5-FU on the proliferative, clonogenic, and apoptotic potential of Hep-2 cells were evaluated with Cell Viability Detection Kit-8, soft agar assay and Annexin VFITC Apoptosis assay, respectively. Migratory and invasive potential of cells was tested using scratch, transwell migration and Matrigel invasion assays. Gene expression of cells exposed to metformin and/or 5-FU was profiled using RT2 mRNA PCR Array plates. Results: Treatment of Hep-2 cells with metformin inhibited cell proliferation by inducing apoptosis, and suppressed cell migration. Besides, treatment of metformin along with 5-FU improved the antiproliferative and anti-migratory effects of 5-FU. However, unexpectedly, metformin was found to enhance cellular invasion and reverse the inhibitory effect of 5-FU on the invasive potential of Hep-2 cells. Conclusion: Our findings suggest that metformin might be used as an adjuvant agent in the treatment of LCa. However, the potential of metformin to promote the invasion of cancer cells should not be neglected.

scholarly journals Evaluation of the Antibacterial and Investigation of the Molecular Docking of New Derivatives of 1, 3, 4-Oxadiazole as Inhibitors of Quorum Sensing System in the Human Pathogen Pseudomonas Aeruginosa

2021 ◽  
Vol 8 (1) ◽  
pp. 27-33
Author(s):  
Sepideh Ghameshlouei ◽  
Nakisa Zarrabi Ahrabi ◽  
Ali Souldozi ◽  
Yasin SarveAhrabi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Docking ◽  
Quorum Sensing ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Chemical Structures ◽  
Sensing System ◽  
Wide Range ◽  
Quorum Sensing System ◽  
Derivatives Of

Background: Oxadiazoles are a group of anti-inflammatory compounds that have a wide range of activity due to their higher efficacy. Pseudomonas aeruginosa is an opportunistic pathogen and a major pathogen of nosocomial infections. This study aimed to evaluate the antibacterial and investigation of the molecular docking of new derivatives of 1, 3, 4-oxadiazole against P. aeruginosa, in vitro & in silico. Materials and Methods: Four new derivatives were synthesized and added to our previous synthetic derivatives of 1, 3, 4-oxadiazole. The antibacterial activity of all derivatives was measured based on three standard species of P. aeruginosa using inhibition zone (IZ) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. Then, employing the computational design of the drug by the molecular docking method, the inhibitory effect of synthetic compounds on the LasR regulatory protein of P. aeruginosa quorum sensing system was investigated, which plays an important role in regulating the expression of pathogenic genes in bacteria. Results: The chemical structures of new compounds were characterized by IR spectra and 1H-NMR. A variety of inhibitory effects were observed by the synthesized compounds – compound 4d and 4g, in particular. Also, the inhibitory effect of these two compounds on the LasR regulatory protein under the control of the quorum sensing system in P. aeruginosa was demonstrated by molecular docking. Conclusions: The results of this study showed that the two compounds containing the functional group of naphthalene and fluorophenyl have a significant effect on the inhibition of P. aeruginosa, as well as on the LasR protein of this bacterium.

Natural prenylated xanthones as potential inhibitors of PI3k/Akt/mTOR pathway in triple negative breast cancer cells

Planta Medica ◽  
2021 ◽  
Author(s):  
Thi Thu Ha Nguyen ◽  
Zhao Qu ◽  
Van Tuyen Nguyen ◽  
Thanh Tra Nguyen ◽  
Thi Tu Anh Le ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Phosphorylated Form ◽  
Anti Cancer ◽  
M Phase ◽  
Potential Inhibitors ◽  
Leading Compounds

Three prenylated xanthones, garcinone E (1), bannaxanthone D (2) and bannanxanthone E (3) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1-3 were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1-3 exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1-3 in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1-3 had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

scholarly journals Novel antimycobacterial C-21 amide derivatives of the antibiotic fusidic acid: synthesis, pharmacological evaluation and rationalization of media-dependent activity using molecular docking studies in the binding site of human serum albumin

MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 961-969 ◽  
Author(s):  
Godwin Akpeko Dziwornu ◽  
Stephanie Kamunya ◽  
Tando Ntsabo ◽  
Kelly Chibale
Keyword(s):  
Molecular Docking ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Natural Product ◽  
Fusidic Acid ◽  
Acid Synthesis ◽  
Docking Studies ◽  
Amide Derivatives ◽  
Dependent Activity ◽  
Derivatives Of

Fusidic acid is a natural product antibiotic used clinically, primarily against staphylococcal infections.

scholarly journals Structure–Activity Relationships and Molecular Docking Analysis of Mcl-1 Targeting Renieramycin T Analogues in Patient-derived Lung Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 875 ◽  
Author(s):  
Korrakod Petsri ◽  
Masashi Yokoya ◽  
Sucharat Tungsukruthai ◽  
Thanyada Rungrotmongkol ◽  
Bodee Nutho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Benzene Ring ◽  
Lung Cancer Cells ◽  
Docking Analysis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Anti Cancer ◽  
Molecular Docking Analysis

Myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2) proteins are promising targets for cancer therapy. Here, we investigated the structure–activity relationships (SARs) and performed molecular docking analysis of renieramycin T (RT) and its analogues and identified the critical functional groups of Mcl-1 targeting. RT have a potent anti-cancer activity against several lung cancer cells and drug-resistant primary cancer cells. RT mediated apoptosis through Mcl-1 suppression and it also reduced the level of Bcl-2 in primary cells. For SAR study, five analogues of RT were synthesized and tested for their anti-cancer and Mcl-1- and Bcl-2-targeting effects. Only two of them (TM-(–)-18 and TM-(–)-4a) exerted anti-cancer activities with the loss of Mcl-1 and partly reduced Bcl-2, while the other analogues had no such effects. Specific cyanide and benzene ring parts of RT’s structure were identified to be critical for its Mcl-1-targeting activity. Computational molecular docking indicated that RT, TM-(–)-18, and TM-(–)-4a bound to Mcl-1 with high affinity, whereas TM-(–)-45, a compound with a benzene ring but no cyanide for comparison, showed the lowest binding affinity. As Mcl-1 helps cancer cells evading apoptosis, these data encourage further development of RT compounds as well as the design of novel drugs for treating Mcl-1-driven cancers.

scholarly journals Synthesis of Azide Functionalized Tetrahydrobenzofurans and their Antineoplastic Study

Folia Medica ◽  
2019 ◽  
Vol 61 (4) ◽  
pp. 551-558
Author(s):  
Chintan Pandit ◽  
Khushal M. Kapadiya
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Biological Activities ◽  
Aromatic Aldehydes ◽  
Inhibitory Effect ◽  
Phenacyl Bromide ◽  
Azide Group ◽  
Anti Cancer ◽  
Comparable Activity ◽  
Derivatives Of

Background: In chemistry, the derivatives of benzofuran which are substituted on five-membered ring constitute one of the salient moieties in medicinal field and a survey of literature revealed that a good number of reports have shown that tetrahydrobenzofuran derivatives are of valuable biological activities. Aim: On the basis of previous survey, we aimed to generate a series of 2-(4-azidobenzoyl)-3-substitutedaryl-6,6-dimethyl-2,3,6,7-tetrahydrobenzofuran-4(5H)-one bearing azide group which were identified by anti-cancer screening against sixteen cell-lines of NCI (National Cancer Institute) using nine different cancer cell panels. Materials and methods: The tetrahydrobenzofuran derivatives were synthesized by multi-component reactions. It was achieved by coupling of dimedone (3.57 mmole), 4-azido phenacyl bromide (3.92 mmole) and various aromatic aldehydes (3.57 mmole) using two different bases i.e. pyridine and N,N- diethylethanamine under reflux condition. Anti-cancer activity was carried out by NCI-60 cell-lines using standard protocol by National Institute of Health. Results: The results from anti-cancer study shows that the compound 4a exhibited diverse cytotoxic activity against renal cancer panel (UO-31) with significant selectivity and had inhibitory effect on the generation of UO-31 (growth percent= 69.36%) and the compound 4e showed comparable activity in the same cell-line (UO-31: growth percent= 80.86%). Conclusions: In summary, a series of azide group containing tetrahydrobenzofuran derivatives have been synthesized and were evaluated for their anticancer activity. It was concluded that the derivatives 4a and 4e exhibited promising anticancer activity. Nature of substituent on phenyl ring seems to be the crucial factor affecting the activity in both the compounds.

Sign in / Sign up

Export Citation Format

Share Document