scholarly journals Synthesis, characterization, and biological evaluation of new spebrutinib analogues: potential candidates with enhanced activity and reduced toxicity profiles

2019 ◽  
Author(s):  
Zaid M Jaber Al-Obaidi ◽  
Omar F Abdul-Rasheed ◽  
Monther F Mahdi ◽  
Ayad M R Raauf
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Cell Line ◽  
Mdck Cell ◽  
Mortality Rates ◽  
Biological Evaluation ◽  
High Morbidity ◽  
Toxicity Profile ◽  
Reduced Toxicity ◽  
Mcf 7

Background: Cancer is regarded as an undoubtable major concern for both researchers and the general public because of its high mortality rates. While breast cancer has the highest incidence of malignancy globally, colon cancer also has high morbidity and mortality rates. Currently, researchers are working on designing, synthesizing, and biologically investigating the effects of some potential anticancer candidates. Methods: The authors successfully synthesized and characterized two potential spebrutinib analogues. These analogues were evaluated with the employment of MCF-7, HCT116, and MDCK cell lines. Results: With respect to the spebrutinib standard, one of these analogues had superior activity against the MCF-7 cell line (IC50; 10.744 µg/mL against 13.566 µg/mL for spebrutinib) and an enhanced toxicity profile on the MDCK cell line (IC50; 8.653 mg/mL against 4.011 mg/mL for spebrutinib).

scholarly journals Synthesis, characterization, and biological evaluation of new spebrutinib analogues: potential candidates with enhanced activity and reduced toxicity profiles

2019 ◽  
Author(s):  
Zaid M Jaber Al-Obaidi ◽  
Omar F Abdul-Rasheed ◽  
Monther F Mahdi ◽  
Ayad M R Raauf
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Cell Line ◽  
Mdck Cell ◽  
Mortality Rates ◽  
Biological Evaluation ◽  
High Morbidity ◽  
Toxicity Profile ◽  
Reduced Toxicity ◽  
Mcf 7

Background: Cancer is regarded as an undoubtable major concern for both researchers and the general public because of its high mortality rates. While breast cancer has the highest incidence of malignancy globally, colon cancer also has high morbidity and mortality rates. Currently, researchers are working on designing, synthesizing, and biologically investigating the effects of some potential anticancer candidates. Methods: The authors successfully synthesized and characterized two potential spebrutinib analogues. These analogues were evaluated with the employment of MCF-7, HCT116, and MDCK cell lines. Results: With respect to the spebrutinib standard, one of these analogues had superior activity against the MCF-7 cell line (IC50; 10.744 µg/mL against 13.566 µg/mL for spebrutinib) and an enhanced toxicity profile on the MDCK cell line (IC50; 8.653 mg/mL against 4.011 mg/mL for spebrutinib).

Biological Evaluation of Newly synthesized Spebrutinibm Analogues: Potential Candidates with Enhanced Activity and Reduced Toxicity Profiles.

2019 ◽  
Vol 9 (o3) ◽  
Author(s):  
Zaid M. Jaber Al-Obaidi ◽  
Omar F. Abdul- Rasheed ◽  
Monther F. Mahdi ◽  
Ayad M.R. M.R. Raauf
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Mdck Cell ◽  
Biological Evaluation ◽  
Toxicity Profile ◽  
Normal Kidney ◽  
Unpublished Work ◽  
Colon Cell ◽  
Reduced Toxicity ◽  
Mcf 7

Background: Undoubtedly, cancer is regarded as a major concern for researchers alongside the whole humanity for its high mortality rates. At this moment, there must be some researchers working hard to design, synthesize, and biologically investigate the effects of some potential candidates to fight back cancer. Materials and methods: In previous unpublished work, the authors successfully designed, synthesized, characterized a potential two spebrutinib analogues. Consequently, these analogues were evaluated with the employment of MCF-7, HCT116, and MDCK cell lines. Results: In respect to the spebrutinib standard, one of these analogues has superior activity against MCF-7 cell line (IC50; 10.744 µg/mL against 13.566 µg/mL for spebrutinib) and an enhanced toxicity profile on MDCK cell line (IC50; 8.653 mg/mL against 4.011 mg/mL for spebrutinib). Conclusion: The two compounds showed good activity against breast and colon cell lines and enhanced toxicity profile against normal kidney cell line in respect to spebrutinib standard.

scholarly journals A New CDK2 Inhibitor with 3-Hydrazonoindolin-2-One Scaffold Endowed with Anti-Breast Cancer Activity: Design, Synthesis, Biological Evaluation, and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 412
Author(s):  
Mohammad M. Al-Sanea ◽  
Ahmad J. Obaidullah ◽  
Mohamed E. Shaker ◽  
Garri Chilingaryan ◽  
Mohammed M. Alanazi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Inhibitory Activity ◽  
Flow Cytometric Analysis ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Intrinsic Activity ◽  
Binding Interaction ◽  
Mcf 7

Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.

scholarly journals Synthesis of Silver-Doxycycline Complex Nanoparticles and Their Biological Evaluation on MCF-7 Cell Line of the Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Vahid Mohammadkarimi ◽  
Negar Azarpira ◽  
Zahra Ghanbarinasab ◽  
Pezhman Shiri ◽  
Fatemeh Sadat Dehghani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Silver Nitrate ◽  
Cell Line ◽  
Biological Evaluation ◽  
Potent Effect ◽  
Different Types ◽  
The Future ◽  
Mcf 7

In the current study, we aim to evaluate the effect of the combination of silver and doxycycline (silver-doxycycline complex) on the viability of the MCF-7 cell line of the breast in comparison with each of them. The Ag-doxycycline NPs were synthesized using silver nitrate and doxycycline solutions. The synthesized Ag-doxycycline NPs were characterized with several analyses. Ag-doxycycline NPs with a concentration of 25 μM is significantly more effective in decreasing the viability of MCF-7 cells than Ag with the same concentration ( P < 0.05 ). Doxycycline with a concentration of 6.25 μM also has a more potent effect on the viability of MCF-7 cells than Ag with the same concentration ( P < 0.05 ). Ag-doxycycline NPs with a 25 μM concentration is more effective than the concentration of 3.125 μM ( P < 0.05 ). Ag-doxycycline NPs were found to be more effective than AgNPs alone in inhibiting the growth of the MCF-7 cells. Also, the increasing utility of nanotechnology in multiple aspects of medicine can lead to using this technology in the treatment of different types of cancer in the future.

Synthesis, Characterization and Biological Evaluation of Indole-Pyrazole Amalgamated α-Cyano Substituted Chalcones

2021 ◽  
Vol 21 ◽  
Author(s):  
Pravin S. Bhale ◽  
Sadanand N. Shringare ◽  
Amol B. Khade ◽  
Hemant V. Chavan
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Safety Margin ◽  
Biological Evaluation ◽  
Biologically Active ◽  
Monkey Cell ◽  
Mcf 7

Background: Indole and pyrazole constitute a major class of biologically active scaffolds. The amalgamation of two or more pharmacophores would generate novel molecular templates that are likely to unveil remarkable biological properties. Objective: An efficient and high yielding synthesis of indole-pyrazole integrated α-cyano substituted chalcones and their in vitro antibreast cancer and antioxidant evaluation. Methods: The synthesis of a series of indole-pyrazole amalgamated α-cyano substituted chalcones (6a-o) was achieved by reacting substituted 3-cyanoacetyl indole 2 with substituted pyrazole aldehyde 5 in the presence of piperidine. All the newly synthesized compounds have been characterized by IR, 1H NMR and HRMS spectroscopy. Results: Anti-breast cancer evaluation of the synthesized compounds in vitro against MCF-7 cell line revealed high anti-breast cancer activities. Amongst the compounds screened 6f, 6g, 6h, 6c, 6d, 6e, 6i and 6k unveiled excellent activity against breast carcinoma (GI50 <0.1µM) as good as adriamycin (GI50 <0.1µM). The compounds were also screened against the normal Vero monkey cell line and the results demonstrated more selectivity against MCF-7. In other hand, compounds, 6b, 6c, 6d, 6h and 6i have shown moderate DPPH and NO radical scavenging activity. Conclusion: Most of the synthesized compounds exhibited significant antitumor activities. These results further support its safety margin by studying the activity on normal Vero monkey cell line. These results acclaim the possible use of these compounds for the design and development of potent anti-breast cancer agents.

scholarly journals The Antiproliferative and Apoptotic Effect of a Novel Synthesized S-Triazine Dipeptide Series, and Toxicity Screening in Zebrafish Embryos

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1170
Author(s):  
Azizah M. Malebari ◽  
Rakia Abd Alhameed ◽  
Zainab Almarhoon ◽  
Muhammad Farooq ◽  
Mohammad A. M. Wadaan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Toxicity Tests ◽  
Therapeutic Drug ◽  
Zebrafish Embryos ◽  
Potential Candidate ◽  
Hek 293 ◽  
Mcf 7

Several derivatives containing morpholine/piperidine, anilines, and dipeptides as pending moieties were prepared using s-triazine as a scaffold. These compounds were evaluated for their anticancer activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231), a colon cancer cell line (HCT-116), and a non-tumorigenic cell line (HEK 293). Tamoxifen was used as a reference. Animal toxicity tests were carried out in zebrafish embryos. Most of these compounds showed a higher activity against breast cancer than colon cancer. Compound 3a—which contains morpholine, aniline, and glycylglycinate methyl ester—showed a high level of cytotoxicity against MCF-7 cells with IC50 values of less than 1 µM. This compound showed a much lower level of toxicity against the non-tumorigenic HEK-293 cell line, and in the in vivo studies using zebrafish embryos. Furthermore, it induced cell cycle arrest at the G2/M phase, and apoptosis in MCF-7 cells. On the basis of our results, 3a emerges as a potential candidate for further development as a therapeutic drug to treat hormone receptor-positive breast cancer.

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