Background: The existence of drug-resistance and lack of selectivity encourages scientists to search
for novel and more selective cytotoxic agents.
Objectives: In this work, novel 1,3,4-triarylpyrazole derivatives were synthesized to study their cytotoxicity on
MCF7 (human breast Cell Line). In addition, QSAR studies were performed to show the relation between the
cytotoxic activity and the structural features of our new synthesized pyrazole derivatives.
Methods: Pyrazole-4-carbaldehyde derivative 3 was utilized as a starting material for the preparation of the new
pyarazole derivatives. These target compounds were screened for their cytotoxic activity against MCF-7 followed
by study cell cycle of the most active compounds. Finally, pharmacophore modeling and QSAR Studies
was carried out.
Results: Among these compounds; 5d and 8b showed the highest anti-proliferative activity (IC50 = 4.9 and 2.11
µM, respectively). Flow cytometric analysis showed that, compounds 5d and 8b arrested the cell cycle in addition
to induction of apoptosis in MCF7 cells. Moreover, their stimulation effect on caspases 3/7 was examined
to explore their mechanism of induction of apoptosis and the results showed that their proapoptotic activity
could be due to the activation of caspases 3/7.
Conclusion: Pyrazole derivatives 5d and 8b displayed potent bioactivities, indicating that these compounds
could be considered as a new lead for more investigation in the future.