Abstract
The balance between cell proliferation and cell growth characterizes tissue homeostasis on one side and cell death on the other side. Fas receptor-mediated apoptosis is a control mechanism for tissue homeostasis, and avoiding this death pathway predisposes to many human diseases, including cancer. Current therapies for this disease are invasive and do not have the desired effect in the control of the disease. In this context, the search for new drugs that contribute to a better treatment is gaining more relevance. 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol (LQM319) [1,2] is a drug currently in preclinical stage, and we have shown that it has a hypertensive effect, similar to captopril, in a hypertensive rat model. Different studies have shown that some chemicals that are used as antihypertensive agents have an antineoplastic effect against certain types of cancer, as is the case of hydralazine [3], and captopril [4], among others [5]. On the other hand, it has been reported that morpholine derivatives may activate Fas (CD95)-mediated apoptosis. The aim of the present study was to show the interaction between CD95 (receptor) and thiomorpholine derivatives (ligand) using molecular modeling and docking studies, and to elucidate the possible action mechanism of 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol.
Highlights
In response to stressful stimuli, cells usually mount a cellular stress response to ensure cell survival [6]
The search for new drugs that contribute to a better treatment is gaining more relevance. 4-tert-butyl-bis-(2,6-thiomorpholin-4-ylmethyl)-1-phenol (LQM319) [1,2] is a drug currently in preclinical stage, and we have shown that it has a hypertensive effect, similar to captopril, in a hypertensive rat model
The molecular docking results suggest a favorable interaction between the CD95 receptor (Apo-1 or Fas) and LQM319 in the pocket of Fas receptor
Summary
In response to stressful stimuli, cells usually mount a cellular stress response to ensure cell survival [6]. Under physiological conditions, this stress response limits tissue damage [7]. Programmed cell death, is an evolutionarily conserved event that eliminates unwanted cells produced during animal development [8,9], and an important mechanism for eliminating tumorigenic cells. Apoptosis plays an important role in homeostasis, immune response, and elimination of abnormal cells [10]. Fas (CD95/Apo-1) has a central role in the physiological regulation of programmed cell death [11]. Apoptosis evasion could be an important step possibly contributing to tumorigenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
