Design, Synthesis and Anticancer Evaluation of Novel Series of Indibulin Analogues

2019 ◽  
Vol 15 (3) ◽  
pp. 231-239
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Seyednasser Ostad ◽  
Shohreh Tavajohi ◽  
Morteza P. Hamedani ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Normal Cell ◽  
Annexin V ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Cancerous Cell ◽  
Ht 29

Background: Cancer is an important cause of human death worldwide. During the last decades, many anticancer agents with anti-tubulin mechanism have been synthesized or extracted from nature and some of them also entered clinical use. Indibulin is one of the most potent tubulin polymerization inhibitors with minimal peripheral neuropathy, which is a big problem by some of the antimitotic agents such as taxanes and vinka alkaloids. With respect to this giant benefit, herein we decided to design and synthesize novel indibulin related compounds and investigate their anticancer activity against HT-29, Caco-2 and T47-D cancerous cell lines as well as NIH-T3T as normal cell line. Objective: The aim of this study was to synthesize new anti-cancer agents and evaluates their cytotoxic activity on diverse cancerous and normal cell lines. Method: Target compounds were synthesized in multistep reaction and cytotoxic activity was investigated by MTT cell viability assay. Results: Herein, nine novel target compounds were synthesized in moderate to good yield. Some of the compounds exerted good cytotoxic activity against cancerous cell lines. Annexin V/PI staining showed that compound 4g could induce apoptosis and necrosis in HT-29 cell line. Conclusion: It is valuable to do further investigation on compound 4g which showed the highest activity against HT-29 and Caco-2 (IC50 values are 6.9 and 7 &µM respectively). Also, synthesis of new derivatives of current synthesized compounds is suggested.

Design, Synthesis and Biological Evaluation of Novel Diaryl Pyrazole Derivatives as Anticancer Agents

2020 ◽  
Vol 17 (3) ◽  
pp. 216-223
Author(s):  
Jalal Nourmahammadi ◽  
Ebrahim Saeedian Moghadam ◽  
Zahra Shahsavari ◽  
Mohsen Amini
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Annexin V ◽  
Biological Evaluation ◽  
Pyrazole Derivatives ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Cancerous Cell

Cancer is one of the major causes of mortality all around the world. Globally, nearly 1 in 6 deaths is due to cancer. Researchers are trying to synthesize new anticancer agents. Previous studies demonstrated that some pyrazole derivatives could be considered as potential anticancer agents. Herein, ten novel derivatives of 1,5-diarylpyrazole were synthesized in four step reactions and cytotoxic activity was investigated by MTT cell viability assay. All of the compounds were characterized by 1H NMR and 13C NMR and their purity was confirmed by elemental analysis. The cytotoxicity was determined against three cancerous cell lines (HT-29, U87MG and MDA-MB 468) and AGO1522 as a normal cell line. Compound 5a showed the best cytotoxic activity on cancerous cell lines in comparison to paclitaxel. Annexin V/ PI staining assay also showed that compounds 5a and 5i would lead to significant apoptosis induction in MDA-MB 486 cell line.

scholarly journals Cytotoxic Activity of Some Spirooxindole-4H-pyran Derivatives

2019 ◽  
pp. 1-6
Author(s):  
Zeinab Faghih ◽  
Zahra Faghih ◽  
Masoomeh Divar ◽  
Soghra Khabnadideh
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Science Research ◽  
Cytotoxic Activities ◽  
Medical Sciences ◽  
Anticancer Properties ◽  
Cancerous Cell ◽  
Mcf 7

Aims: Isatin is a honored scaffold and one of the most favorable class of heterocyclic systems that possesses many interesting biological activities and well-tolerated in humans. Here a series of fifteen spirooxindole-4H-pyran derivatives containing both isatin and pyran moieties (ICa-ICo) will be examine for their anti-cancer activity. Study Design: Cytotoxic evaluation of some spirooxindole-4H-pyran derivatives in two cancerous cell lines.  Place and Duration of Study: Pharmaceutical Science Research Center and Shiraz Institute for Cancer Research, Medical School in Shiraz University of Medical Sciences, Shiraz, Iran, between June 2018 and July 2019. Methodology: MTT assay was used to evaluate the cytotoxic activities of these compounds. The anticancer properties of the tested compounds were determined using A549 and MCF-7 cell lines. Results: Among the tested compounds ICc, ICd and ICf showed the best cytotoxic activities  against both cancerous cell lines. Compounds ICh and ICj showed desirable cytotoxic activities against A549 cell line. Compound ICb showed desirable cytotoxic activities against MCF-7 cell line. Conclusion: We conclude that the isatin-linked pyran analog can serve as a prototype molecule for further development of a new class of anticancer agents.

Assessment of anti-cancer effects of koenimbine on colon cancer cells

2020 ◽  
Vol 28 (3) ◽  
pp. 185-190
Author(s):  
Maliheh Astaneh ◽  
Soudeh Ghafouri-Fard ◽  
Zahra Fazeli ◽  
Zahra Taherian-Esfahani ◽  
Sepideh Dashti ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Colon Cancer Cells ◽  
Cytotoxic Effects ◽  
Anti Cancer ◽  
Ht 29

BACKGROUND: Recent studies have highlighted the role of natural elements in reduction of cancer cell growth and apoptosis. Koenimbine, a natural product isolated from Murraya koenigii (L) Spreng is a substance with cytotoxic effects on cancer cells. AIM: The effects of koenimbine on HT-29 and SW48 colon cancer cells were evaluated by MTT and Annexin V assays. Expression levels of Wnt/β-catenin pathway genes were quantified by real time PCR. RESULTS: The IC50 values of koenimbine in HT-29 and SW48 was calculated to be 50 μg/ml based on the results of MTT assay. This value was 75 μg/ml in IEC-18 cells which were used as normal control. Annexin V assays revealed induction of cell apoptosis and necrosis in HT-29 and SW48 cells but not IEG18 cells by koenimbine. Koenimbin treatment resulted in significant down-regulation of CYCLD1 expression in SW48 cell line, but up-regulation of this gene in HT29 cell line. Expression of TBLR1, DKK1, GSK3B and β-catenin was significantly decreased after koenimbin treatment in HT-19 cell line. Moreover, expression of DKK1 and GSK3B was significantly decreased after koenimbin treatment in SW-40 cell line. TCF4 expression was not detected in any of cell lines either before or after treatment with koenimbin. CONCLUSION: The current in vitro study showed the cytotoxic effects of koenimbin on two colon cancer cell lines and the effects of this substance on expression of selected genes from Wnt-β catenin pathway. Future in vivo studies are needed before suggestion of this substance as an anti-cancer drug.

scholarly journals Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Perumal Gobinath ◽  
Ponnusamy Packialakshmi ◽  
Daoud Ali ◽  
Saud Alarifi ◽  
Amal Alotaibi ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Normal Cell ◽  
Biological Activities ◽  
Research Work ◽  
Indole Derivatives ◽  
Spike Glycoprotein ◽  
Standard Drug

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a–1j, was synthesized without a catalyst. The products were confirmed by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC50−0.9 μm, MCF−7, LC50−0.55 μm, HeLa, LC50−0.50 μm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC50 > 100 μg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score −2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus.

scholarly journals The Evaluation of Antiproliferative Effect of Imatinib derivatives Against Breast and Colon Cell-Lines

2013 ◽  
Vol 11 (01) ◽  
pp. 74-82
Author(s):  
Ali N. Hussein ◽  
Omar F. Abdul- Rasheed ◽  
Monther F. Mahdi ◽  
Ayad M R Raauf
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Mdck Cell ◽  
Kinase Inhibitors ◽  
Hct116 Cell ◽  
Antiproliferative Effects ◽  
Cancerous Cell ◽  
Colon Cell ◽  
Mcf 7

Background: Cancer is considered as one of the major leading causes of death. Tyrosine kinase inhibitors are recognized for their potential antiproliferative effects. Materials and methods: In the previous study, the authors designed, synthesized, and characterized two imatinib derivatives. These derivatives were biologically evaluated with the utilization of MCF-7, HCT116, and MDCK cell lines. Results: In respect to the imatinib standard, compound 2b has superior activity against HCT116 cell line (IC50; 15.88 μg/mL against 18.52 μg/mL for imatinib) and an improved cytotoxic activity on MDCK cell line (IC50; 0.654 mg/mL against 0.272 mg/mL for imatinib). Conclusion: The two synthesized compounds showed biological activity against cancerous cell lines and improved cytotoxic activity against normal non-cancerous cell line with respect to the imatinib standard.

Design, Synthesis and In vitro Cytotoxicity of New 1,2,3-triazol- and Nitrostyrene Hybrids as Potent Anticancer Agents

2018 ◽  
Vol 16 (2) ◽  
pp. 213-219
Author(s):  
Zahra Tashrifi ◽  
Maryam Mohammadi-khanaposhtani ◽  
Mehdi Shafiee Ardestani ◽  
Maliheh Safavi ◽  
Kurosh Rad-Moghadam ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Click Reaction ◽  
L929 Cell ◽  
Staining Technique ◽  
In Vitro Cytotoxicity ◽  
Standard Drug

Background: A new series of 1,2,3-triazol-nitrostyrene derivatives was designed, synthesized, and evaluated for cytotoxic activity against Hep-2 and L929 cell lines. </P><P> Methods: The synthetic procedure started from the functionalization of 4-hydroxybenzaldehyde with propargyl bromide and a subsequent click reaction to give 1,2,3-triazole derivatives. Then, the reaction of the mentioned derivatives with nitromethane led to the formation of the title compounds in excellent yields. Results: Most of the compounds exhibited better cytotoxic activity with respect to the standard drug 5-fluorouracil. Among them, (E)-1-(3,4-dichlorobenzyl)-4-((4-(2-nitrovinyl)phenoxy)methyl)-1H- 1,2,3-triazole 6i (IC50 = 4.66 &#177; 1.3 &#181;M) against the Hep-2 cell line and (E)-1-(2,3-dichlorobenzoyl)- 4-((4-(2-nitrovinyl)phenoxy)methyl)-1H-1,2,3-triazole 6g (IC50 = 5.18 &#177; 0.8 &#181;M) against the L929 cell line exhibited the best cytotoxic effects. Conclusion: Moreover, the acridine orange/ethidium bromide double staining technique showed that the most potent compounds 6i and 6g could induce apoptosis in studied cancer cell lines.

scholarly journals Chemical composition and cytotoxic activity of the essential oils of Cymbopogon citratus L. Grown in phu tho province

2018 ◽  
Vol 14 (4) ◽  
pp. 683-687 ◽  
Author(s):  
Hoang Thi Kim Van ◽  
Nguyen Minh Quy ◽  
Do Thi Vinh Ha ◽  
Nguyen Thanh Hai ◽  
Hoang Thi Ly ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Essential Oils ◽  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Hep3b Cell ◽  
Cytotoxicity Test ◽  
Cymbopogon Citratus ◽  
Ic50 Values

Culms and leaves of Cymbopogon citratus L. were collected from two regions of Phu Tho province (Thanh Son and Phu Ninh) and used as materials for essential oil extraction. Oils obtained were steam-distilled, analyzed for chemical composition and evaluated for cytotoxic activity against three different cancer cell lines. The GC/MS analysis showed that citral is the major content of the steam-distilled essential oils which was found in the range of 64.15-76.22%. Camphene was found only in culm oils of both regions but it was not detected in the leaf oils. Interestingly, the isomer forms of ocimene present at higher content in the culm oils than in the leaf oils whereas myrcene content in the leaf oils is higher than that in the culm oils. In a cytotoxicity test, four essential oils of culms and leaves of C. citratus from Thanh Son and Phu Ninh showed potent activity against A549 (human lung carcinoma) cell line with the IC50 values ranging from 4.01±0.39 to 6.3±0.54 µg/ml. The essential oils (culms and leaves) from Phu Ninh exhibited moderate effects on the Hela (human cervical adenocarcinoma) cells with the IC50 values of 19.43±1.16 and 42±2.41 µg/ml, respectively. However, they were inactive against the human hepatocellular carcinoma Hep3B cell line. The essential oils from Thanh Son exhibited potent cytotoxic activity against Hela and Hep3B cell lines with the IC50 values ranging from 1.18±0.26 to 8.91±0.32 µg/ml. The results indicated that the essential oils of C. citratus from Thanh Son, Phu Tho could be considered as a promising candidate for the natural sources of anticancer agents.

scholarly journals Synthesis, and Biological Evaluations of Novel Pyrazinoic Acid Derivatives as Anticancer Agents

2021 ◽  
Author(s):  
Shiva Akhlaghi ◽  
Azar mostoufi ◽  
Hadi kalantar ◽  
Masood Fereidoonnezhad
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Dna Cleavage ◽  
Dependent Manner ◽  
Mobility Shift ◽  
Gel Mobility Shift ◽  
Ht 29 ◽  
Pyrazinoic Acid ◽  
Mcf 7

Abstract Pyrazinoic acid or pyrazine-2-carboxylic acid (PA), due to its nitrogenous heteroaromatic ring, can be explored as an anticancer agent. Here, a series of twenty novels PA derivatives have been synthesized and characterized using IR, NMR, and mass spectrums. Their cytotoxic activity was evaluated against three different cancer cell lines, including lung (A549), breast (MCF-7), and colon (HT-29). P16, the most potent compound, showed moderate cytotoxicity with IC50 of 6.11 μM, 10.64 μM, and 14.92 μM, against the A549, MCF-7, and HT-29 cell lines, respectively. Furthermore, the effect of this compound against MRC5 as a non-tumoral lung cell line, exhibited a selectivity index of 9.02. The apoptotic induction activity of P16 was also performed on the A549 cell line. The results showed that as the concentration of the compound increases (from 3 to 6 μM), the percentage of induction of apoptosis increases from 8.54% to 72.4%. Electrophoretic gel mobility shift assays showed that P16 was also able to ROS induce DNA cleavage in the presents of H2O2 (1.0 mM) in dose-dependent manner. Molecular docking was also applied to anticipate the binding locations and the binding of the synthesized compound with Bcl-2 apoptosis regulator and DNA as their proposed targets.

Anticancer Activity and In silico ADMET Properties of 2,4,5- Trisubstitutedthiazole Derivatives

2020 ◽  
Vol 21 ◽  
Author(s):  
Bilal A. Al-Jaidi ◽  
Soha Taher Telfah ◽  
Sanaa K. Bardaweel ◽  
Pran Kishore Deb ◽  
Pobitra Borah ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Thiazole Ring ◽  
Active Compounds ◽  
In Silico Admet

Background: Recently, a series of 15 compounds with 2,4,5-trisubstitutedthiazole scaffold having 2- amino/amido/ureido functional groups attached with 5-aryl and 4-carboxylic acid/ester groups (1-15) were reported from our research group as novel potential inhibitors of carbonic anhydrase III (CA III) enzyme. Several research studies revealed the potential role of CA inhibitors as anticancer agents, giving us the impetus to further explore these compounds for their potential as anticancer agents. Objectives: The objective of this study is to investigate the potential of 2,4,5-trisubstitutedthiazole derivatives (1-15) for their possible cytotoxic activity (in vitro) and to calculate (in silico) the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to evaluate the drug-likeness of these compounds. Methods: Cytotoxic activity (in vitro) was carried out on two breast cancer cell lines (MCF7 and MDA231), and lymphoblastoid human erythroleukemia cell line (K562) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as a positive control. ADMET properties were calculated (in silico) using QikProp module of Schrodinger. Results: Compounds 6 and 9 with a phenylureido group at 2-position, and a methyl-carboxylate moiety at 4-position having para-tolyl and benzyl moiety, respectively at the 5-position of the thiazole ring showed significant cytotoxicity against all the three cell lines. In particular, compound 6 with para-tolyl group at 5-position, exhibited most potent inhibitory effect on the viability of MCF7, MDA231 and K562 cells, with IC50 values of 22, 26 and 11 µM, respectively. Notably, all the highly active compounds possess phenyluriedo group at 2-position with a methyl ester group at 4-position, indicating the probable role of these substituents in the target interaction and inducing cytotoxicity. Interestingly, compounds 1-4 and 10-13 with a free amino group at 2-position did not show any cytotoxic effect on K562 cell line, while exhibiting mild to moderate cytotoxicity against the MCF7 and MDA231 cell lines. However, none of the tested compounds showed any activity against normal human dermal fibroblast cells indicating the safety/tolerability of the examined concentrations. Furthermore, these compounds also exhibited satisfactory ADMET properties (in silico), without violating the Lipinski’s rule of five. Conclusion: The most active compounds 6 and 9 predicted to have good oral absorption and low human serum protein binding, exhibiting no reactive functional group and probable CNS activity compared with 95% of the known oral drugs as predicted (in silico) by QikProp. Thus, compounds 6 and 9 can be considered as lead molecules for further modification and discovery of novel anticancer agents with nanomolar potency.

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.

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