Investigation of podophyllotoxin esters as potential anticancer agents: Synthesis, biological studies and tubulin inhibition properties

Mohd Adil Shareef; Divya Duscharla; G. Ramasatyaveni; Neha R. Dhoke; Amitava Das; Ramesh Ummanni; Ajay Kumar Srivastava

doi:10.1016/j.ejmech.2014.10.050

Investigation of podophyllotoxin esters as potential anticancer agents: Synthesis, biological studies and tubulin inhibition properties

Mohd Adil Shareef, Divya Duscharla, G. Ramasatyaveni, Neha R. Dhoke, Amitava Das, Ramesh Ummanni, Ajay Kumar Srivastava

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	128-137
Number of pages	10
Journal	European journal of medicinal chemistry
Volume	89
DOIs	https://doi.org/10.1016/j.ejmech.2014.10.050
State	Published - Jan 7 2015
Externally published	Yes

Keywords

Anticancer agents
CA-4
Podophyllotoxin
Tubulin polymerization inhibition

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2014.10.050

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@article{958e08c8194d4ceba960843ab01cc4f9,

title = "Investigation of podophyllotoxin esters as potential anticancer agents: Synthesis, biological studies and tubulin inhibition properties",

abstract = "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.",

keywords = "Anticancer agents, CA-4, Podophyllotoxin, Tubulin polymerization inhibition",

author = "Shareef, {Mohd Adil} and Divya Duscharla and G. Ramasatyaveni and Dhoke, {Neha R.} and Amitava Das and Ramesh Ummanni and Srivastava, {Ajay Kumar}",

note = "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: {\textcopyright} 2014 Elsevier Masson SAS. All rights reserved.",

year = "2015",

month = jan,

day = "7",

doi = "10.1016/j.ejmech.2014.10.050",

language = "English (US)",

volume = "89",

pages = "128--137",

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publisher = "Elsevier Masson SAS",

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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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Investigation of podophyllotoxin esters as potential anticancer agents: Synthesis, biological studies and tubulin inhibition properties

Abstract

Keywords

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