Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Tubulin Polymerization ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Colchicine Binding Site ◽  
Anti Cancer

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.

Synthesis, evaluation of biological activity, docking and molecular dynamic studies of pyrimidine derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Shahin Boumi ◽  
Jafar Moghimirad ◽  
Massod Amanlou ◽  
Seyed Nasser Ostad ◽  
Shohreh Tavajohi ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Docking Studies ◽  
Cytotoxic Activities ◽  
Tubulin Polymerization ◽  
Pyrimidine Derivatives ◽  
Aryl Group ◽  
Colchicine Binding Site

Background: The microtubule is composed of αβ-tubulin heterodimers and is an attractive target for the design of anticancer drugs. Over the years, various compounds have been developed and their effect on tubulin polymerization has been studied. Despite a great efforts to make an effective drug, no drug has been introduced which inhibit colchicine binding site. Objective: In the current work a series of pyrimidine derivatives were designed and synthesized. Furthermore their cytotoxic activities were evaluated and molecular docking studies were performed. Methods: Twenty compounds of pyrimidine were synthesized in 2 different groups. In the first group, 4,6-diaryl pyrimidine was connected to the third aryl group via thio-methylene spacer. In the second group, this linker was substituted by S-CH2- triazole moiety. The cytotoxic activity of these compounds was evaluated against 4 different cell lines (HT-29, MCF-7, T47D, NIH3T3). Results: Compounds 6d, 6m, 6p showed potent cytotoxic activity against MCF7 cancerous cell lines. Between these compounds, compound 6p did not show cytotoxic activity against NIH- 3T3 (normal cell) cell line. Docking studies show that these compounds occupy colchicine binding site in tubulin protein and probably their anticancer mechanism is inhibition of tubulin polymerization. Conclusion : Altogether, with respect to obtained results, it is attractive and beneficial to further investigation on pyrimidine scaffold as antimitotic agents. Attention to the selectivity index of 6p on MCF7 cell line could be valuable in design new chemical agents for treatment of breast cancer.

scholarly journals Design, eco-friendly synthesis, molecular modeling and anticancer evaluation of thiazol-5(4H)-ones as potential tubulin polymerization inhibitors targeting the colchicine binding site

RSC Advances ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 2791-2811 ◽  
Author(s):  
Abeer M. El-Naggar ◽  
Ibrahim H. Eissa ◽  
Amany Belal ◽  
Amira A. El-Sayed
Keyword(s):  
Molecular Modeling ◽  
Cancer Treatment ◽  
Binding Site ◽  
Therapeutic Approach ◽  
Tubulin Polymerization ◽  
Colchicine Binding Site ◽  
Tubulin Polymerization Inhibitors

In recent years, suppressing tubulin polymerization has been developed as a therapeutic approach for cancer treatment.

scholarly journals Differential Responses of Colorectal Cancer Cell Lines to Enterococcus faecalis’ Strains Isolated from Healthy Donors and Colorectal Cancer Patients

2019 ◽  
Vol 8 (3) ◽  
pp. 388 ◽  
Author(s):  
Carolina De Almeida ◽  
Matteo Lulli ◽  
Vincenzo di Pilato ◽  
Nicola Schiavone ◽  
Edda Russo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Line ◽  
Enterococcus Faecalis ◽  
Cell Lines ◽  
Healthy Subjects ◽  
Intestinal Cell ◽  
Proliferation Index ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Healthy Donors

The metabolites produced by the host’s gut microbiota have an important role in the maintenance of intestinal homeostasis, but can also act as toxins and induce DNA damage in colorectal epithelial cells increasing the colorectal cancer (CRC) chance. In this scenario, the impact of some of the components of the natural human gastrointestinal microbiota, such as Enterococcus faecalis (E. faecalis), at the onset of CRC progression remains controversial. Since under dysbiotic conditions it could turn into a pathogen, the aim of this study was to compare the effect of E. faecalis’ strains (isolated from CRC patients and healthy subjects’ stools) on the proliferation of different colorectal cells lines. First, we isolated and genotyping characterized the Enterococcus faecalis’ strains. Then, we analyzed the proliferation index (by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay) of three tumor and one normal intestinal cell lines, previously exposed to E. faecalis strains pre-cultured medium. Stool samples of CRC patients demonstrated a reduced frequency of E. faecalis compared to healthy subjects. In addition, the secreted metabolites of E. faecalis’ strains, isolated from healthy donors, decreased the human ileocecal adenocarcinoma cell line HCT-8 and human colon carcinoma cell line HCT-116 cell proliferation without effects on human colorectal adenocarcinoma cell line SW620 and on normal human diploid cell line CLR-1790. Notably, the metabolites of the strains isolated from CRC patients did not influence the cell growth of CRC cell lines. Our results demonstrated a new point of view in the investigation of E. faecalis’ role in CRC development, which raises awareness of the importance of not only associating the presence/absence of a unique microorganism, but also in defining the specific characteristics of the different investigated strains.

scholarly journals Characterization of a New Small Bowel Adenocarcinoma Cell Line and Screening of Anti-Cancer Drug against Small Bowel Adenocarcinoma

2015 ◽  
Vol 185 (2) ◽  
pp. 550-562 ◽  
Author(s):  
Hirobumi Suzuki ◽  
Yoshihiro Hirata ◽  
Nobumi Suzuki ◽  
Sozaburo Ihara ◽  
Kosuke Sakitani ◽  
...  
Keyword(s):  
Small Bowel ◽  
Cell Line ◽  
Cancer Drug ◽  
Small Bowel Adenocarcinoma ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Anti Cancer

scholarly journals Stipa tenacissima L.: A New Promising Source of Bioactive Compounds with Antioxidant and Anticancer Potentials

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 757
Author(s):  
Mehdi El Bouchti ◽  
Mohammed Bourhia ◽  
Amal Alotaibi ◽  
Kaoutar Aghmih ◽  
Sanaa Majid ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Bioactive Compounds ◽  
Antioxidant Properties ◽  
Antiproliferative Effect ◽  
Adenocarcinoma Cell Line ◽  
Stipa Tenacissima ◽  
Adenocarcinoma Cell ◽  
Ic50 Values ◽  
Ht 29

Background: Stipa tenacissima L. (S. tenacissima), called Esparto grass, is a cultivated species used for industrial purposes, including textile production. This species has never been studied for its medical potential before, nor has it been used in traditional medicines. It is thus fitting that the present study aimed to investigate the pharmacological potential of S. tenacissima. To achieve this goal, this work was conducted to study the chemical composition, antioxidant properties, and antiproliferative effects of S. tenacissima against cancerous cell lines, including the human colorectal adenocarcinoma cell line (HT-29) and human breast adenocarcinoma cell line (MDA-MB-231). Fractionation and characterization of S. tenacissima extract showed the presence of promising bioactive fractions. The fractions obtained from S. tenacissima extract exhibited interesting antioxidant properties, with IC50 values ranging from 1.26 to 1.85 mg/mL. All fractions, such as F1, F2, F3, and F4, induced an important antiproliferative effect on the cancer cell lines MDA-MB-231, scoring IC50 values ranging from 63.58 ± 3.14 to 99.880 ± 0.061 µg/mL. These fractions (F1, F2, F3, and F4) also exhibited a potent antiproliferative effect versus HT-29 cell lines, with IC50 values ranging from 71.50 ± 4.97 to 87.500 ± 1.799 µg/mL. Therefore, S. tenacissima could constitute a new natural source of bioactive compounds that can be used for therapeutic purposes to fight cancer and free radical damage.

Cytotoxic Activity and Apoptosis Induction by Gaillardin

2013 ◽  
Vol 68 (3-4) ◽  
pp. 108-112 ◽  
Author(s):  
Maryam Hamzeloo Moghadam ◽  
Farzaneh Naghibi ◽  
Azadeh Atoofi ◽  
Mitra Asgharian Rezaie ◽  
Mahboobeh Irani ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Breast Adenocarcinoma ◽  
Adenocarcinoma Cell Line ◽  
Cell Lung Carcinoma ◽  
Adenocarcinoma Cell ◽  
Mcf 7

Cytotoxic activity of gaillardin, a sesquiterpene lactone isolated from Inula oculus-christi L. (Asteraceae), was assessed in the human breast adenocarcinoma cell line MCF-7, human hepatocellular carcinoma cell line HepG-2, human non-small cell lung carcinoma cell line A-549, and human colon adenocarcinoma cell line HT-29, resulting in IC50 values of 6.37, 6.20, 4.76, and 1.81 μg/mL, respectively, in the microculture tetrazolium-formazan MTT assay. In vitro apoptosis-inducing properties of gaillardin were also evaluated in MCF-7 cells with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling (TUNEL) assay. The results suggest gaillardin as a candidate for further studies in cancer therapy

Sign in / Sign up

Export Citation Format

Share Document