TY - JOUR
T1 - Investigation of podophyllotoxin esters as potential anticancer agents
T2 - Synthesis, biological studies and tubulin inhibition properties
AU - Shareef, Mohd Adil
AU - Duscharla, Divya
AU - Ramasatyaveni, G.
AU - Dhoke, Neha R.
AU - Das, Amitava
AU - Ummanni, Ramesh
AU - Srivastava, Ajay Kumar
N1 - Funding Information:
Authors acknowledge Director CSIR-IICT for support and financial assistance by CSIR, Govt. of India, New Delhi under 12th Five-year plan projects: ACT ( CSC-0301 ) and (SMiLE CSC-0111 ). Fellowships provided by CSIR, UGC and ICMR are gratefully acknowledged by MAS and DD (CSIR-JRF), RG (UGC-JRF) and ND (ICMR-JRF). Authors thank Dr. Ahmed Kamal for his generous support by providing podophyllotoxin resin and valuable suggestions during the progress of the project.
Publisher Copyright:
© 2014 Elsevier Masson SAS. All rights reserved.
PY - 2015/1/7
Y1 - 2015/1/7
N2 - A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8g-h, 8m and 8o showed IC50 values in the range of 0.71-10.94 μM. Among compounds, 8g and 8h showed significant cytotoxicity towards all the types of cancer studied. Cell cycle analysis revealed that the compounds 8a, 8m and 8o inhibit proliferation by cell cycle arrest. Also Hoechst-positive nucleus indicating apoptosis of these cells was observed in presence of 8g-h. Further studies revealed that these compounds inhibit tubulin polymerization and leads to the inactivation of AKT/PKB that are known to play an important role in the proliferation of cancer cells.
AB - A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8g-h, 8m and 8o showed IC50 values in the range of 0.71-10.94 μM. Among compounds, 8g and 8h showed significant cytotoxicity towards all the types of cancer studied. Cell cycle analysis revealed that the compounds 8a, 8m and 8o inhibit proliferation by cell cycle arrest. Also Hoechst-positive nucleus indicating apoptosis of these cells was observed in presence of 8g-h. Further studies revealed that these compounds inhibit tubulin polymerization and leads to the inactivation of AKT/PKB that are known to play an important role in the proliferation of cancer cells.
KW - Anticancer agents
KW - CA-4
KW - Podophyllotoxin
KW - Tubulin polymerization inhibition
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U2 - 10.1016/j.ejmech.2014.10.050
DO - 10.1016/j.ejmech.2014.10.050
M3 - Article
C2 - 25462233
AN - SCOPUS:84908465470
SN - 0223-5234
VL - 89
SP - 128
EP - 137
JO - European journal of medicinal chemistry
JF - European journal of medicinal chemistry
ER -