scholarly journals Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4957
Author(s):  
Wanda Baer-Dubowska ◽  
Maria Narożna ◽  
Violetta Krajka-Kuźniak

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.

2021 ◽  
pp. 30-39
Author(s):  
Prateek Paul ◽  
Manvi .

For prostaglandin production, the enzyme cyclooxygenase (COX) is required. The two COX isoforms are constitutive COX-1 (which is responsible for physiological functions) and inducible COX-2 (involved in inflammation). COX inhibition explains both the medicinal (inhibition of COX-2) and negative effects (inhibition of COX-1) effects of non-steroidal anti-inflammatory medicines (NSAIDs). Nonsteroidal anti-inflammatory medicines (NSAIDs) act by blocking the enzyme cyclooxygenase (COX), which produces prostaglandins (PGs). To a greater or lesser extent, they share similar side effects, such as stomach and renal toxicity. According to a recent study, there are at least two COX isoenzymes. COX-1 is a naturally occurring enzyme that creates prostaglandins (PGs), which protect the stomach and kidneys. Aspirin's well-known anti-cancer impact could also be related to its influence on COX-2, which is expressed in this condition. As a result, selective COX-2 inhibitors may have new therapeutic potential as anticancer drugs, as well as in preventing premature labor and maybe reducing the progression of Alzheimer's disease.


2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.


2021 ◽  
Vol 23 (3) ◽  
Author(s):  
V. V. Buheruk ◽  
O. B. Voloshyna ◽  
L. I. Kovalchuk ◽  
I. V. Balashova ◽  
O. V. Naidionova

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.


RSC Advances ◽  
2014 ◽  
Vol 4 (54) ◽  
pp. 28756-28764 ◽  
Author(s):  
Amit Anthwal ◽  
Kundan Singh ◽  
M. S. M. Rawat ◽  
Amit K. Tyagi ◽  
Bharat B. Aggarwal ◽  
...  

The C5-curcumin-dithiocarbamate analogues were synthesized in search of new molecules with anti-proliferation potential against cancer cells. These new compounds demonstrated higher anti-proliferation and anti-inflammatory activity against cancer cell lines in comparison to curcumin.


2020 ◽  
Vol 8 (6) ◽  
pp. 327-327 ◽  
Author(s):  
Chengfei Yang ◽  
Jing Luo ◽  
Xing Luo ◽  
Weisheng Jia ◽  
Zhenqiang Fang ◽  
...  

Endocrine ◽  
2016 ◽  
Vol 55 (1) ◽  
pp. 209-214 ◽  
Author(s):  
Junko Sato ◽  
Toyoyoshi Uchida ◽  
Koji Komiya ◽  
Hiromasa Goto ◽  
Kageumi Takeno ◽  
...  

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