1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase

Mei Jung Lai; Ritu Ojha; Mei Hsiang Lin; Yi Min Liu; Hsueh Yun Lee; Tony Eight Lin; Kai Cheng Hsu; Chi Yen Chang; Mei Chuan Chen; Kunal Nepali; Jang Yang Chang; Jing Ping Liou

doi:10.1016/j.ejmech.2018.10.066

1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase

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

Abstract

We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC₅₀ value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC₅₀ value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.

Original language	English
Pages (from-to)	612-630
Number of pages	19
Journal	European Journal of Medicinal Chemistry
Volume	162
DOIs	https://doi.org/10.1016/j.ejmech.2018.10.066
Publication status	Published - Jan 15 2019

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Benzamide
Cancer
HDAC
Indoline
Tubulin

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2018.10.066

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@article{b165987ce366440e9ca720ade9aa379c,

title = "1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase",

abstract = "We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.",

keywords = "Benzamide, Cancer, HDAC, Indoline, Tubulin",

author = "Lai, \{Mei Jung\} and Ritu Ojha and Lin, \{Mei Hsiang\} and Liu, \{Yi Min\} and Lee, \{Hsueh Yun\} and Lin, \{Tony Eight\} and Hsu, \{Kai Cheng\} and Chang, \{Chi Yen\} and Chen, \{Mei Chuan\} and Kunal Nepali and Chang, \{Jang Yang\} and Liou, \{Jing Ping\}",

note = "Funding Information: This research were supported by the Ministry of Science and Technology, Taiwan (grant no. MOST 103-2113-M-038-001-MY3 , 107-2113-M-038-001 ). Publisher Copyright: {\textcopyright} 2018",

year = "2019",

month = jan,

day = "15",

doi = "10.1016/j.ejmech.2018.10.066",

language = "English",

volume = "162",

pages = "612--630",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

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T1 - 1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase

AU - Lai, Mei Jung

AU - Ojha, Ritu

AU - Lin, Mei Hsiang

AU - Liu, Yi Min

AU - Lee, Hsueh Yun

AU - Lin, Tony Eight

AU - Hsu, Kai Cheng

AU - Chang, Chi Yen

AU - Chen, Mei Chuan

AU - Nepali, Kunal

AU - Chang, Jang Yang

AU - Liou, Jing Ping

PY - 2019/1/15

Y1 - 2019/1/15

N2 - We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.

AB - We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.

KW - Benzamide

KW - Cancer

KW - HDAC

KW - Indoline

KW - Tubulin

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UR - https://www.scopus.com/pages/publications/85056813873#tab=citedBy

U2 - 10.1016/j.ejmech.2018.10.066

DO - 10.1016/j.ejmech.2018.10.066

M3 - Article

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VL - 162

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JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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