Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers

N. Sankara Rao; V. Lakshma Nayak; A. V. Subba Rao; S. M. Ali Hussaini; Satish Sunkari; Abdullah Alarifi; Ahmed Kamal

doi:10.1016/j.arabjc.2016.07.014

Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers

N. Sankara Rao, V. Lakshma Nayak, A. V. Subba Rao, S. M. Ali Hussaini, Satish Sunkari, Abdullah Alarifi, Ahmed Kamal

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

Abstract

A series of cinnamido-propionone conjugates (4–6a-h and 7a-f) has been designed, synthesized and evaluated for their anticancer potential against some human cancer cell lines. Among them, conjugates 6d and 6g have shown significant cytotoxic activity against prostate cancer cells (DU-145) displaying IC₅₀ of 7.48 and 8.91 μM respectively. Studies to understand the mechanism of action of 6d and 6g indicate that they inhibit the tubulin polymerization thereby arresting the cell cycle in G2/M phase. Furthermore, studies such as mitochondrial membrane potential and Annexin V-FITC assay suggested that these conjugates 6d and 6g induced cell death by apoptosis. The molecular docking studies suggested that the binding by these conjugates takes place at the colchicine site of the tubulin protein.

Original language	English (US)
Pages (from-to)	4740-4755
Number of pages	16
Journal	Arabian Journal of Chemistry
Volume	12
Issue number	8
DOIs	https://doi.org/10.1016/j.arabjc.2016.07.014
State	Published - Dec 2019
Externally published	Yes

Keywords

Apoptosis
Cinnamides
Cytotoxicity
Tubulin polymerization inhibitors

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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10.1016/j.arabjc.2016.07.014

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@article{4f34c349ac6142a49361869921a89df2,

title = "Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers",

abstract = "A series of cinnamido-propionone conjugates (4–6a-h and 7a-f) has been designed, synthesized and evaluated for their anticancer potential against some human cancer cell lines. Among them, conjugates 6d and 6g have shown significant cytotoxic activity against prostate cancer cells (DU-145) displaying IC50 of 7.48 and 8.91 μM respectively. Studies to understand the mechanism of action of 6d and 6g indicate that they inhibit the tubulin polymerization thereby arresting the cell cycle in G2/M phase. Furthermore, studies such as mitochondrial membrane potential and Annexin V-FITC assay suggested that these conjugates 6d and 6g induced cell death by apoptosis. The molecular docking studies suggested that the binding by these conjugates takes place at the colchicine site of the tubulin protein.",

keywords = "Apoptosis, Cinnamides, Cytotoxicity, Tubulin polymerization inhibitors",

author = "{Sankara Rao}, N. and {Lakshma Nayak}, V. and {Subba Rao}, {A. V.} and {Ali Hussaini}, {S. M.} and Satish Sunkari and Abdullah Alarifi and Ahmed Kamal",

note = "Funding Information: N.S.R, A.V.S, and S.M.A.H thank CSIR-New Delhi for the award of senior research. We acknowledge funding received from the project entitled “Affordable Cancer Therapeutics (ACT)” under XIIth five year plan. This project was also supported by College of Science Research Centre, Deanship of Scientific Research at King Saud University. Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2019",

month = dec,

doi = "10.1016/j.arabjc.2016.07.014",

language = "English (US)",

volume = "12",

pages = "4740--4755",

journal = "Arabian Journal of Chemistry",

issn = "1878-5352",

publisher = "King Saud University",

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}

TY - JOUR

T1 - Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers

AU - Sankara Rao, N.

AU - Lakshma Nayak, V.

AU - Subba Rao, A. V.

AU - Ali Hussaini, S. M.

AU - Sunkari, Satish

AU - Alarifi, Abdullah

AU - Kamal, Ahmed

N1 - Funding Information: N.S.R, A.V.S, and S.M.A.H thank CSIR-New Delhi for the award of senior research. We acknowledge funding received from the project entitled “Affordable Cancer Therapeutics (ACT)” under XIIth five year plan. This project was also supported by College of Science Research Centre, Deanship of Scientific Research at King Saud University. Publisher Copyright: © 2016 The Authors

PY - 2019/12

Y1 - 2019/12

N2 - A series of cinnamido-propionone conjugates (4–6a-h and 7a-f) has been designed, synthesized and evaluated for their anticancer potential against some human cancer cell lines. Among them, conjugates 6d and 6g have shown significant cytotoxic activity against prostate cancer cells (DU-145) displaying IC50 of 7.48 and 8.91 μM respectively. Studies to understand the mechanism of action of 6d and 6g indicate that they inhibit the tubulin polymerization thereby arresting the cell cycle in G2/M phase. Furthermore, studies such as mitochondrial membrane potential and Annexin V-FITC assay suggested that these conjugates 6d and 6g induced cell death by apoptosis. The molecular docking studies suggested that the binding by these conjugates takes place at the colchicine site of the tubulin protein.

AB - A series of cinnamido-propionone conjugates (4–6a-h and 7a-f) has been designed, synthesized and evaluated for their anticancer potential against some human cancer cell lines. Among them, conjugates 6d and 6g have shown significant cytotoxic activity against prostate cancer cells (DU-145) displaying IC50 of 7.48 and 8.91 μM respectively. Studies to understand the mechanism of action of 6d and 6g indicate that they inhibit the tubulin polymerization thereby arresting the cell cycle in G2/M phase. Furthermore, studies such as mitochondrial membrane potential and Annexin V-FITC assay suggested that these conjugates 6d and 6g induced cell death by apoptosis. The molecular docking studies suggested that the binding by these conjugates takes place at the colchicine site of the tubulin protein.

KW - Apoptosis

KW - Cinnamides

KW - Cytotoxicity

KW - Tubulin polymerization inhibitors

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Arylcinnamido-propionone conjugates as tubulin polymerization inhibitors and apoptotic inducers

Abstract

Keywords

ASJC Scopus subject areas

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