Copper-Catalyzed Syntheses of Pyrene-Pyrazole Pharmacophores
and Structure Activity Studies for Tubulin Polymerization
Dinabandhu Sar
Indrajit Srivastava
Santosh K. Misra
Fatemeh Ostadhossein
Parinaz Fathi
Dipanjan Pan
10.1021/acsomega.8b00320.s001
https://acs.figshare.com/articles/journal_contribution/Copper-Catalyzed_Syntheses_of_Pyrene-Pyrazole_Pharmacophores_and_Structure_Activity_Studies_for_Tubulin_Polymerization/6509684
Tubulin polymerization is critical
in mitosis process, which regulates
uncontrolled cell divisions. Here, we report a new class of pyrene-pyrazole
pharmacophore (PPP) for targeting microtubules. Syntheses of seven
pyrenyl-substituted pyrazoles with side-chain modification at N-1
and C-3 positions of the pyrazole ring were accomplished from alkenyl
hydrazones via C–N dehydrogenative cross-coupling using copper
catalyst under aerobic condition. Tubulin polymerization
with PPPs was investigated using docking and biological tools to reveal
that these ligands are capable of influencing microtubule polymerization
and their interaction with α-, β-tubulin active binding
sites, which are substituent specific. Furthermore, cytotoxicity response
of these PPPs was tested on cancer cells of different origin, such
as MCF-7, MDA-MB231, and C32, and also noncancerous normal cells,
such as MCF-10A. All newly synthesized PPPs showed excellent anticancer
activities. The anticancer activities and half-maximal inhibitory
concentration (IC<sub>50</sub>) values of all PPPs across different
cancer cell lines (MCF-7, MDA-MB231, and C32) have been demonstrated.
1,3-Diphenyl-5-(pyren-1-yl)-1<i>H</i>-pyrazole was found
to be best among all other PPPs in killing significant population
of all of the cancerous cell with IC<sub>50</sub> values 1 ±
0.5, 0.5 ± 0.2, and 5.0 ± 2.0 μM in MCF-7, MDA-MB231,
and C32 cells, respectively.
2018-06-13 13:58:49
C 32 cells
anticancer activities
MDA-MB
Structure Activity Studies
Tubulin Polymerization Tubulin polymerization
-10A
PPP
C -3 positions
cancer cell lines
pyrazole
IC
MCF