Penfluridol as a Candidate of Drug Repurposing for Anticancer Agent

Tuan, Nguyen Minh; Lee, Chang Hoon

doi:10.3390/molecules24203659

Cited by 22 publications

(13 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data in UCB are in line with the observed antineoplastic effects of CADs in other solid tumors [11][12][13][14][15][16][17]. Other antineoplastic mechanisms of this class of compounds may also play a role, including antimigratory and invasion effects, cell cycle effects, changes in cholesterol homeostasis, autophagy, immune modulation, or nonhomologous end joining (reviewed in {Shaw, 2019 #2068} [25][26][27][28].…”

Section: Discussionsupporting

confidence: 82%

“…Strikingly, a class of commonly used antidepressants, antihistamines, and antipsychotics-the so-called cationic amphiphilic drugs (CADs)-were previously found to preferentially induce cell death in transformed cells [11]. The most potent CADs, including penfluridol, display preferential cytotoxicity toward transformed cells in vitro and potent antitumor activity even as single agents in murine tumor models (among others in breast, colon, pancreatic, and lung carcinoma) [11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Thus, there would be almost none side effects occurred. Recently, by drug repurposing, some studies reported that PF can inhibit tumor growth and metastasis in glioblastoma, breast cancer cells, pancreas, and lung cancer cells (Chien et al, 2015;Ranjan et al, 2016Ranjan et al, , 2017Tuan & Lee, 2019). Therefore, those could also be the underlying mechanisms of PF against E. faecalis biofilms.…”

Section: Discussionmentioning

confidence: 99%

“…PF, available since the 1970 s, is a long-acting oral antipsychotic agent, used to treat acute psychosis (van Praag et al, 1971) and schizophrenia (Soares & Lima, 2006). A single weekly oral of 30 mg (~12.5 to 25 mg/kg for mouse model) was used to treat acute psychoses in patients without side effects occurred (van Praag et al, 1971). And >60 mg/day (~25 to 50 mg/kg for mouse model) was also used for the treatment of schizophrenia (Soares & Lima, 2006).…”

Section: Discussionmentioning

confidence: 99%

Drug repurposing: Antimicrobial and antibiofilm effects of penfluridol against Enterococcus faecalis

et al. 2020

View full text Add to dashboard Cite

The bacterium Enterococcus faecalis has increasingly attracted global attention as an important opportunistic pathogen due to its ability to form biofilms that are known to increase drug resistance. However, there are still no effective antibiofilm drugs in clinical settings. Here, by drug repurposing, we investigated the antibacterial activity of penfluridol (PF), an oral long‐acting antipsychotic approved by the FDA, against E. faecalis type strain and its clinical isolates. It was found that PF inhibited the growth of E. faecalis planktonic cells with the MIC and MBC of 7.81 µg/ml and 15.63 ~ 62.50 µg/ml, respectively. Moreover, PF could significantly prevent the biofilm formation of E. faecalis at the concentration of 1 × MIC. Furthermore, PF significantly eradicated 24 h pre‐formed biofilms of E. faecalis in a dose‐dependent manner, with a concentration range of 1 × MIC to 8 × MIC. Here, through the checkerboard method with other tested conventional antibiotics, we also determined that gentamycin, penicillin G, and amikacin showed partial synergistic antibacterial effects with PF. Also, PF showed almost no hemolysis on human erythrocytes. In a mouse peritonitis model, a single dose of 20 mg/kg of PF treatment could significantly reduce the bacterial colonization in the liver (~5‐fold reduction) and spleen (~3‐fold reduction). In conclusion, these findings indicated that after structural optimization, PF has the potential as a new antibacterial agent against E. faecalis.

show abstract

“…effects in patients with glioblastoma and pancreatic cancer, suggesting immunooncological properties [22].…”

Section: The Two-hit Paradigm: Excessive Angiotensin II (Ang Ii) and Loss Of Angiotensin (1-7) (Ang 1-7) Generate Oxidative Stress Both Dmentioning

confidence: 99%

COVID-19: A Catalyst for Novel Psychiatric Paradigms - Part 1

Sfera¹,

Osorio²,

Maldonado³

et al. 2022

Biotechnology to Combat COVID-19

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in the late 2019 and spread rapidly throughout the world, becoming a pandemic in March 2020. It became obvious early that the prognosis of this illness is highly variable, ranging from few mild symptoms to severe complications and death, indicating that aside from the pathogen virulence, host factors contribute significantly to the overall outcome. Like SARS-CoV and Human Coronavirus NL63 (HCoV-NL63-NL63), SARS-CoV-2 enters host cells via several receptors among which angiotensin converting enzyme-2 (ACE-2) are the most studied. As this protein is widely expressed in the lungs, blood vessels, brain, kidney, testes and ovaries, the effects of this virus are widespread, affecting many body tissues and organs. Viral attachment to ACE-2 downregulates this protein, disrupting angiotensin II (ANG II) hydrolysis that in return contributes to the unchecked accumulation of this peptide. ANG II toxicity is the result of excessive activation of ANG II type 1 receptors (AT-1Rs) and N-methyl-D-aspartate NMDA receptors (NMDARs). Overstimulation of these proteins, along with the loss of angiotensin (1–7) (ANG 1–7), upregulates reactive oxygen species (ROS), inflicting end-organ damage (hit 1). However, a preexistent redox impairment may be necessary for the development of SARS-CoV-2 critical illness (hit 2). Here we propose a two-hit paradigm in which COVID-19 critical illness develops primarily in individuals with preexistent antioxidant dysfunction. Several observational studies are in line with the two hit model as they have associated poor COVID-19 prognosis with the hereditary antioxidant defects. Moreover, the SARS-CoV-2 interactome reveals that viral antigen NSP5 directly inhibits the synthesis of glutathione peroxidase (GPX), an antioxidant enzyme that along with glucose-6-phosphate dehydrogenase (G6PD) protect the body from oxidative damage. Indeed, individuals with G6PD deficiency have less favorable COVID-19 outcomes compared to the general population.

show abstract

Penfluridol as a Candidate of Drug Repurposing for Anticancer Agent

Cited by 22 publications

References 97 publications

Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer

Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer

Drug repurposing: Antimicrobial and antibiofilm effects of penfluridol against Enterococcus faecalis

COVID-19: A Catalyst for Novel Psychiatric Paradigms - Part 1

Contact Info

Product

Resources

About