Rayavarapu, S.,Yarla, N. S.,Kadiri, S. K.,Bishayee, A.,Vidavalur, S.,Tadikonda, R.,Basha, M.,Pidugu, V. R.,Dowluru, Ksvgk,Lakappa, D. B.,Kamal, M. A.,Md Ashraf, G.,Tarasov, V. V.,Chubarev, V. N.,Klochkov, S. G.,Barreto, G. E.,Bachurin, S. O.,Aliev, G.

2017

August

Sci Repsci Rep

Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities

Published

()

Antineoplastic Agents/chemistry/*pharmacology Apoptosis/drug effects Cell Line, Tumor Cell Proliferation/drug effects Esters Glycosides/chemistry/*pharmacology Humans MCF-7 Cells Molecular Structure Phenol/chemistry/*pharmacology

7

11

8309

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 microM, but they are less cytotoxic on normal cells (IC50 > 100 microM). 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.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 microM, but they are less cytotoxic on normal cells (IC50 > 100 microM). 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.

2045-2322 (Electronic) 20

2017/08/18

http://www.ncbi.nlm.nih.gov/pubmed/28814788http://www.ncbi.nlm.nih.gov/pubmed/28814788

10.1038/s41598-017-05832-w