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.

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.

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.

scholarly journals Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

2021 ◽  
Author(s):  
ulviye acar çevik ◽  
Ismail Celik ◽  
Ayşen IŞIK ◽  
Yusuf Özkay ◽  
Zafer Asım Kaplancıklı
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Evaluation Studies ◽  
Biological Evaluation ◽  
Binding Modes ◽  
Anticancer Activities ◽  
Mcf 7

Abstract In this study, due to the potential anticancer effects of the benzimidazole ring system, a series of benzimidazole-1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, 13C NMR, and MS spectra analyses. In the in vitro anticancer assay, all the compounds tested anticancer activities using MTT-based assay against five cancer cell lines (MCF-7, A549, HeLa, C6, and HepG2). Among them, compound 5a exhibited the most potent activity with IC50 values of 5,165±0,211 μM and 5,995±0,264 μM against MCF-7 and HepG2 cell lines. Compound 5a was included in the BrdU test to determine the DNA synthesis inhibition effects for both cell types. Furthermore, compound 5c was also found to be more effective than doxorubicin on the HeLa cell line. The selectivity of anticancer activity was evaluated in NIH3T3 (mouse embryo fibroblast cell line) cell line. In vitro, enzymatic inhibition assays of aromatase enzyme were performed for compound 5a acting on the MCF-7 cell line. For compound 5a, in silico molecular docking against aromatase enzyme was performed to determine possible protein-ligand interactions and binding modes.

scholarly journals Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents

2019 ◽  
Vol 12 (4) ◽  
pp. 169
Author(s):  
Anne Cecília Nascimento da Cruz ◽  
Dalci José Brondani ◽  
Temístocles I´talo de Santana ◽  
Lucas Oliveira da Silva ◽  
Elizabeth Fernanda da Oliveira Borba ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Cell Cycle Progression ◽  
Annexin V ◽  
Biological Evaluation ◽  
G1 Phase ◽  
Cellular Functions ◽  
Ic50 Values ◽  
Annexin V Assay

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM).

Design, Synthesis and Biological Evaluation of a Novel Series of Thiadiazole-Based Anticancer Agents as Potent Angiogenesis Inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Burcugül Altuğ-Tasa ◽  
Betül Kaya-Çavuşoğlu ◽  
Ayşe T. Koparal ◽  
Gülhan Turan ◽  
Ali S. Koparal ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Evaluation ◽  
Tube Formation ◽  
In Vivo Studies ◽  
Human Cancer Cell Lines ◽  
Ic50 Values

Background: Thiadiazole has attracted a great deal of interest as a versatile heterocycle for the discovery and development of potent anticancer agents. Thiadiazole derivatives exert potent antitumor activity against a variety of human cancer cell lines through various mechanisms. Objective: The goal of this work was to design and synthesize thiadiazole-based anticancer agents with anti-angiogenic activity. Methods: N-aryl-2-[(5-(aryl)amino-1,3,4-thiadiazol-2-yl)thio]acetamides (4a-r) were synthesized via the reaction of 5-(aryl)amino-1,3,4- thiadiazole-2(3H)-thiones with N-(aryl)-2-chloroacetamides in the presence of potassium carbonate. The compounds were investigated for their cytotoxic effects on three cancer (A549, HepG2, SH-SY5Y), two normal (HUVEC and 3T3-L1) cell lines using MTT and WST1 assays. In order to examine whether the compounds have anti-angiogenic effects or not, HUVEC were cultured on matrigel matrix to create a vascular-like tube formation. Results: Compounds 4d, 4m and 4n were more effective on A549 human lung adenocarcinoma cells than cisplatin. The IC50 values of compounds 4d, 4m and 4n for A549 cell line were found to be 7.82±0.4, 12.5±0.22, 10.1±0.52 µM, respectively when compared with cisplatin (IC50= 20±0.51 µM), whilst their IC50 values for HUVEC cell line were determined as 138.7±0.84, 78±0.44, 177.6±0.2 µM, respectively after 48 h treatment. The concentrations (10-20-50 µM) of compounds 4d, 4e, 4l, 4m, 4n, 4q and 4r were found to inhibit vascular like tube formation. Conclusion: According to their anticancer and anti-angiogenic effects, compounds 4d, 4m and 4n may be potential anticancer agents for further in vivo studies.

Synthesis and Biological Evaluation of New 1,3,4-Oxadiazoles as Potential Anticancer Agents and Enzyme Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 914-921 ◽  
Author(s):  
Leyla Yurttaş ◽  
Betül K. Çavuşoğlu ◽  
Gülşen A. Çiftçi ◽  
Halide E. Temel
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Enzyme Inhibitors ◽  
A549 Cells ◽  
Fibroblast Cell ◽  
Biological Evaluation ◽  
Rat Glioma ◽  
Human Lung Carcinoma ◽  
Nih 3T3

Background: 1,3,4-Oxadiazoles have been known with a wide variety of pharmacological activities including anticancer activity. Objective: In this study, novel 2,5-disubstituted 1,3,4-oxadiazole derivatives were synthesized and evaluated for determining their anticancer, anticholinesterase and lipoxygenase (LOX) inhibitory activity. Methods: All compounds were tested against C6 rat glioma, A549 human lung carcinoma and NIH/3T3 mouse embryo fibroblast cell lines to define cytotoxic concentrations and apoptosis induction levels which they cause. Results: Many of the compounds exhibited remarkable potency that compounds 2a, 2b, 2e, 2h and 2j against C6 cells and compounds 2a, 2b, 2d, 2g, 2i, 2j against A549 cells were found more active than cisplatin. Compound 2d namely, 2-[(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)thio]-1-(4-chlorophenyl)ethan-1-one induced apoptosis of A549 cells with 74.9% whereas cisplatin caused 70.9% percentage. Conclusion: Among them, compounds 2d and 2j against A549 cell line, compounds 2b and 2e against both tumor cell lines showed selective cytotoxicity evaluating the inhibition concentration against NIH/3T3 cell line. None of the compounds showed significant acetylcholinesterase (AChE) and lipoxygenase inhibitory activities.

scholarly journals Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1613 ◽  
Author(s):  
Angelika A. Adamus-Grabicka ◽  
Magdalena Markowicz-Piasecka ◽  
Marcin Cieślak ◽  
Karolina Królewska-Golińska ◽  
Paweł Hikisz ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Dna Cleavage ◽  
Cancer Cell Lines ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Proliferative Potential ◽  
Monoclinic System

A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds’ activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.

Synthesis, Biological Evaluation and Docking Study of New Pyrimidine Compounds as Anticancer Agents

Drug Research ◽  
2020 ◽  
Author(s):  
Shahin Boumi ◽  
Jafar Moghimirad ◽  
Seyed Nasser Ostad ◽  
Massoud Amanlou ◽  
Shohreh Tavajohi ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Docking Study ◽  
Biological Evaluation ◽  
Cytotoxic Activities ◽  
Aryl Group ◽  
The Third ◽  
Colchicine Binding Site

Abstract Objectives 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. Methods 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. Twelve compounds of pyrimidine were synthesized in 3 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 sulfoxide-methylene moiety and in the third group sulfone-methylene group was used as spacer. Results The cytotoxic activity of these compounds were evaluated against 3 different cancerous cell lines (HT-29, MCF-7, T47D) as well as normal cell line (NIH3T3). Compounds in group 2 showed the best cytotoxicity and compound 7d showed the most potent cytotoxic activity against all cell lines. Molecular modelling studies revealed that compound 7d could strongly bind to the colchicine binding site of tubulin. Conclusion Altogether, with respect to obtained results, it is attractive and beneficial to further investigation on pyrimidine scaffold as antimitotic agents.

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 Biological Evaluation of a Novel Series of Indole-3- Carboxamide Derivatives for Cancer Treatment as EGFR Inhibitors

2018 ◽  
Vol 15 (1) ◽  
pp. 70-83 ◽  
Author(s):  
Lan Zhang ◽  
Xin-Shan Deng ◽  
Guang-Peng Meng ◽  
Chao Zhang ◽  
Cong-Chong Liu ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Egfr Inhibitors ◽  
Target Compound ◽  
Anticancer Activities ◽  
Aberrant Expression

Background: As reported EGFR is a sialoglycoprotein with tyrosine kinase activity involved in control of cellular survival, multiplication, differentiation and metastasis. Dysregulation or aberrant expression of EGFR has been implicated in cell transformation and having oncogenic roles in a number of human cancers. Therefore EGFR has become a significant target for developing targeted therapy for cancer. Methods: A novel series of indole-3-carboxamide derivatives as EGFR inhibitors were designed, synthesized and evaluated for the anticancer activity in vitro against three EGFR high-expressed cancer cell lines (A549, HeLa, and SW480), one EGFR low-expressed cell line (HepG2) and one human liver normal cell line (HL7702) by MTT assay. Results: The target compounds 6c, 6f, 6i, 6j, 6l, 6r, 6u and 6x exhibited potent anticancer activities against the three tested cancer cell lines and weak cytotoxic effects on HepG2, which imply that the target compounds are probably effective in inhibiting EGFR. And they also did not show measurable activities in HL7702, which imply the target compounds are likely to overcome the nonspecific toxicity against normal cells. Particularly, the target compound 6x indicated equal to the positive control erlotinib. In addition, molecular docking studies demonstrated the target compound 6x may be the potential inhibitor to EGFR. Conclusion: A new EGFR inhibitor scaffold and a preliminary discussion on their SARs provide promising opportunities to guide further research on indole-3-carboxamide derivatives as novel anticancer agents.

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