TY - JOUR
T1 - 1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles
T2 - Exhibiting anticancer activity through intracellular ROS scavenging and the mitochondria-dependent death pathway
AU - Alex, Jimi M.
AU - Singh, Sandeep
AU - Kumar, Raj
N1 - Publisher Copyright:
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - A series of 17 analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1 to JP-17) bearing two aromatic rings at positions 3 and 5, either of which ought to be heterocyclic, were synthesized and evaluated for their anti-proliferative potential against breast cancer (MCF-7 and T-47D) and lung cancer (H-460 and A-549) cell lines for the first time. JP-1-7, -10, -11, -14, and -15 were observed to exhibit significant anti-proliferative activity against MCF-7 cells. Some notions about structure-activity relationships are reported. The investigated compounds were found to lower the intracellular reactive oxygen species in the H2DCFDA assay and also caused mitochondria-dependent cell death in the MCF-7 cell line, indicating a plausible mechanism of their anticancer effect. Analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1-17) were synthesized and evaluated for their anti-proliferative activity in four cancer cell lines and for their intracellular ROS scavenging properties. An attempt was made to determine the mitochondrial membrane potential of MCF-7 cells treated with JP-1 and -14, aiming to elucidate the mechanism by which proliferation was curbed.
AB - A series of 17 analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1 to JP-17) bearing two aromatic rings at positions 3 and 5, either of which ought to be heterocyclic, were synthesized and evaluated for their anti-proliferative potential against breast cancer (MCF-7 and T-47D) and lung cancer (H-460 and A-549) cell lines for the first time. JP-1-7, -10, -11, -14, and -15 were observed to exhibit significant anti-proliferative activity against MCF-7 cells. Some notions about structure-activity relationships are reported. The investigated compounds were found to lower the intracellular reactive oxygen species in the H2DCFDA assay and also caused mitochondria-dependent cell death in the MCF-7 cell line, indicating a plausible mechanism of their anticancer effect. Analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1-17) were synthesized and evaluated for their anti-proliferative activity in four cancer cell lines and for their intracellular ROS scavenging properties. An attempt was made to determine the mitochondrial membrane potential of MCF-7 cells treated with JP-1 and -14, aiming to elucidate the mechanism by which proliferation was curbed.
KW - Antiproliferative
KW - MCF cell lines
KW - Mitochondria-dependent cell death
KW - Pyrazoles
KW - Synthesis
UR - http://www.scopus.com/inward/record.url?scp=84908049543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908049543&partnerID=8YFLogxK
U2 - 10.1002/ardp.201400199
DO - 10.1002/ardp.201400199
M3 - Article
C2 - 25139842
AN - SCOPUS:84908049543
SN - 0365-6233
VL - 347
SP - 717
EP - 727
JO - Archiv der Pharmazie
JF - Archiv der Pharmazie
IS - 10
ER -