TY - JOUR
T1 - Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities
AU - Rayavarapu, Srinuvasarao
AU - Yarla, Nagendra Sastry
AU - Kadiri, Sunanda Kumari
AU - Bishayee, Anupam
AU - Vidavalur, Siddaiah
AU - Tadikonda, Ramu
AU - Basha, Mahaboob
AU - Pidugu, Vijaya Rao
AU - Dowluru, Kaladhar S.V.G.K.
AU - Lakappa, Dhananjaya Bhadrapura
AU - Kamal, Mohammad A.
AU - Md Ashraf, Ghulam
AU - Tarasov, Vadim V.
AU - Chubarev, Vladimir N.
AU - Klochkov, Sergey G.
AU - Barreto, George E.
AU - Bachurin, Sergey O.
AU - Aliev, Gjumrakch
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4.43 ± 0.35 to 49.63 ± 3.59 μM, but they are less cytotoxic on normal cells (IC50 > 100 μM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC50 of 6.13 ± 0.64 and 4.43 ± 0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.
AB - A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4.43 ± 0.35 to 49.63 ± 3.59 μM, but they are less cytotoxic on normal cells (IC50 > 100 μM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC50 of 6.13 ± 0.64 and 4.43 ± 0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.
UR - http://www.scopus.com/inward/record.url?scp=85027525486&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-05832-w
DO - 10.1038/s41598-017-05832-w
M3 - Article
C2 - 28814788
AN - SCOPUS:85027525486
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 8309
ER -
