scholarly journals Conjugation of Diclofenac with Novel Oleanolic Acid Derivatives Modulate Nrf2 and NF-κB Activity in Hepatic Cancer Cells and Normal Hepatocytes Leading to Enhancement of Its Therapeutic and Chemopreventive Potential

2021 ◽  
Vol 14 (7) ◽  
pp. 688
Author(s):  
Maria Narożna ◽  
Violetta Krajka-Kuźniak ◽  
Barbara Bednarczyk-Cwynar ◽  
Małgorzata Kucińska ◽  
Robert Kleszcz ◽  
...  

Combining NSAIDs with conventional therapeutics was recently explored as a new strategy in cancer therapy. Our earlier studies showed that novel oleanolic acid oximes (OAO) conjugated with aspirin or indomethacin may enhance their anti-cancer potential through modulation of the Nrf2 and NF-κB signaling pathways. This study focused on the synthesis and biological evaluation of four diclofenac (DCL)–OAO derivative conjugates in the context of these pathways’ modification and hepatic cells survival. Treatment with the conjugates 4d, 3-diclofenacoxyiminoolean-12-en-28-oic acid morpholide, and 4c, 3-diclofenacoxyiminoolean-12-en-28-oic acid benzyl ester significantly reduced cell viability in comparison to the DCL alone. In THLE-2, immortalized normal hepatocytes treated with these conjugates resulted in the activation of Nrf2 and increased expression in SOD-1 and NQO1, while the opposite effect was observed in the HepG2 hepatoma cells. In both cell lines, reduced activation of the NF-κB and COX-2 expression was observed. In HepG2 cells, conjugates increased ROS production resulting from a reduced antioxidant defense, induced apoptosis, and inhibited cell proliferation. In addition, the OAO morpholide derivative and its DCL hybrid reduced the tumor volume in mice bearing xenografts. In conclusion, our study demonstrated that conjugating diclofenac with the OAO morpholide and a benzyl ester might enhance its anti-cancer activity in HCC.

2019 ◽  
Vol 6 (9) ◽  
pp. 190125 ◽  
Author(s):  
Lifang Yang ◽  
Xuemei Qin ◽  
Hongcun Liu ◽  
Yanye Wei ◽  
Hailiang Zhu ◽  
...  

A series of novel resveratrol derivatives were designed, synthesized and evaluated as anti-cancer agents. Most of the compounds showed significant anti-proliferative activities against three human cancer cell lines (HepG2, A549 and Hela). Among these compounds, compound r displayed the most potent inhibitory activity and showed low cytotoxic activity. Cell apoptosis and cell cycle assays demonstrated that compound r significantly induced apoptosis ( p < 0.001) and arrested cell cycle at S phase. Immunofluorescence microscopy analysis showed compound r disrupted the tubulin network. Docking simulations supported the pharmacological results of compound r . It is believed that this work would be very useful for designing a new series of tubulin inhibitors.


2017 ◽  
Vol 27 (9) ◽  
pp. 1923-1928 ◽  
Author(s):  
Suresh Poudapally ◽  
Shankar Battu ◽  
Loka Reddy Velatooru ◽  
Murali Satyanarayana Bethu ◽  
Venkateswara Rao Janapala ◽  
...  

MedChemComm ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 1377-1385 ◽  
Author(s):  
Xiaojuan Xu ◽  
Senzhen Wang ◽  
Yuan Chang ◽  
Chaochao Ge ◽  
Xinna Li ◽  
...  

Compound 3c induced apoptosis and autophagy and inhibited the migration of hepatoma cells depending on ROS generation.


2019 ◽  
Vol 164 ◽  
pp. 706-716 ◽  
Author(s):  
Ying-Ying Zhong ◽  
Hui-Sheng Chen ◽  
Pan-Pan Wu ◽  
Bing-Jie Zhang ◽  
Yang Yang ◽  
...  

2020 ◽  
Author(s):  
Lifang Guo ◽  
Benshan Xu ◽  
Zirui Wan ◽  
Lulu Ren ◽  
Jie Zhang ◽  
...  

Abstract Background: A series of aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione were synthesized. The chemical structures of the desired compounds were identified by 1H NMR, ESI-MS and elementary analytical. The anti-cancer and anti-angiogenesis activities of the newly synthesized compounds were evaluated by proliferation and migration assays, respectively. Results: The screening results demonstrated that compounds 2 and 5 showed potent anti-tumor activity (IC50 values ranging from 7.1 to 15.9μM) with low cytotoxic activities (IC50>79.3μM). Although compound 5 showed little effects on endothelia proliferation (IC50=65.3μM), it indeed significantly abrogated endothelia cell migration (IC50=6.7μM). Conclusions: This work may impart new direction for the investigations of aryl-piperazine derivatives and lead to the development of potent novel anti-tumor and anti-angiogenesis agents.


2020 ◽  
Author(s):  
Lifang Guo ◽  
Benshan Xu ◽  
Zirui Wan ◽  
Lulu Ren ◽  
Jie Zhang ◽  
...  

Abstract Background: A series of aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.0 2,6 ] dec-8-ene-3,5-dione were synthesized. The chemical structures of the desired compounds were identified by 1 H NMR, ESI-MS and elementary analytical. The anti-cancer and anti-angiogenesis activities of the newly synthesized compounds were evaluated by proliferation and migration assays, respectively. Results: The screening results demonstrated that compounds 2 and 5 showed potent anti-tumor activity (IC 50 values ranging from 7.1 to 15.9μM) with low cytotoxic activities (IC 50 > 79.3μM). Although compound 5 showed little effects on endothelia proliferation (IC 50 =65.3μM), it indeed significantly abrogated endothelia cell migration (IC 50 =6.7μM). Conclusions: This work may impart new direction for the investigations of aryl-piperazine derivatives and lead to the development of potent novel anti-tumor and anti-angiogenesis agents.


RSC Advances ◽  
2020 ◽  
Vol 10 (50) ◽  
pp. 30223-30237
Author(s):  
Prasanta Das ◽  
Sarah Boone ◽  
Dipanwita Mitra ◽  
Lindsay Turner ◽  
Ritesh Tandon ◽  
...  

The synthetic efficacy and biological relevance extend an opportunity to further drug-discovery development of fluoro-spiro-isoxazolines as novel anti-viral and anti-cancer agents.


Sign in / Sign up

Export Citation Format

Share Document