Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines

Ahmed Kamal; Kokkonda Sreekanth; P. Praveen Kumar; Nagula Shankaraiah; G. Balakishan; M. Janaki Ramaiah; S. N.C.V.L. Pushpavalli; Paramita Ray; Manika Pal Bhadra

doi:10.1016/j.ejmech.2010.01.054

Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines

Ahmed Kamal, Kokkonda Sreekanth, P. Praveen Kumar, Nagula Shankaraiah, G. Balakishan, M. Janaki Ramaiah, S. N.C.V.L. Pushpavalli, Paramita Ray, Manika Pal Bhadra

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

27 Scopus citations

Abstract

New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.

Original language	English (US)
Pages (from-to)	2173-2181
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	45
Issue number	6
DOIs	https://doi.org/10.1016/j.ejmech.2010.01.054
State	Published - Jun 2010
Externally published	Yes

Bibliographical note

Funding Information:
We are thankful to the National Cancer Institute (NCI), USA for providing the data in the 57-cell panel of human cancer cell lines. The authors K.S, P.P.K and G.B.K are also grateful to CSIR, New Delhi, for the award of Research Fellowships.

Keywords

Anticancer activity
Apoptosis
DNA binding affinity
G1 cell cycle arrest
Phenanthrylphenol
Pyrrolobenzodiazepines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2010.01.054

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title = "Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines",

abstract = "New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.",

keywords = "Anticancer activity, Apoptosis, DNA binding affinity, G1 cell cycle arrest, Phenanthrylphenol, Pyrrolobenzodiazepines",

author = "Ahmed Kamal and Kokkonda Sreekanth and Kumar, {P. Praveen} and Nagula Shankaraiah and G. Balakishan and Ramaiah, {M. Janaki} and Pushpavalli, {S. N.C.V.L.} and Paramita Ray and Bhadra, {Manika Pal}",

note = "Funding Information: We are thankful to the National Cancer Institute (NCI), USA for providing the data in the 57-cell panel of human cancer cell lines. The authors K.S, P.P.K and G.B.K are also grateful to CSIR, New Delhi, for the award of Research Fellowships.",

year = "2010",

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doi = "10.1016/j.ejmech.2010.01.054",

language = "English (US)",

volume = "45",

pages = "2173--2181",

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AU - Sreekanth, Kokkonda

AU - Kumar, P. Praveen

AU - Shankaraiah, Nagula

AU - Balakishan, G.

AU - Ramaiah, M. Janaki

AU - Pushpavalli, S. N.C.V.L.

AU - Ray, Paramita

AU - Bhadra, Manika Pal

N1 - Funding Information: We are thankful to the National Cancer Institute (NCI), USA for providing the data in the 57-cell panel of human cancer cell lines. The authors K.S, P.P.K and G.B.K are also grateful to CSIR, New Delhi, for the award of Research Fellowships.

PY - 2010/6

Y1 - 2010/6

N2 - New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.

AB - New phenanthrylphenol-pyrrolobenzodiazepine (PP-PBD) conjugates have been synthesized and evaluated for their biological activity. One of the compounds 4a has been evaluated for its antiproliferative activity on 57 human tumour cell lines. The growth inhibition of 4a-c has been determined by MTT viability assay on MCF-7 cell line. Among them, 4c showed most potent growth inhibition. Based on this, an attempt was made to rationalize their mechanism of action through cell cycle analysis and DNA interaction studies. The effect of the lead compound 4c on MCF-7 cell growth associated with cell cycle arrest in G1 phase, followed by apoptosis. Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation.

KW - Anticancer activity

KW - Apoptosis

KW - DNA binding affinity

KW - G1 cell cycle arrest

KW - Phenanthrylphenol

KW - Pyrrolobenzodiazepines

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Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines

Abstract

Bibliographical note

Keywords

UN SDGs

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