Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents

Jing Ping Liou, Neeraj Mahindroo, Chun Wei Chang, Fu Ming Guo, Sandy Wen Hsing Lee, Uan Kang Tan, Teng Kuang Yeh, Ching Chuan Kuo, Yi Wei Chang, Ping Hsun Lu, Yen Shih Tung, Ke Ta Lin, Jang Yang Chang, Hsing Pang Hsieh

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the 3-carbonyl linker. The SAR information revealed that the methoxy group of the B ring could be replaced with an electron-donating group such as methyl (in compound 9) or N,N-dimethylamino (in compound 13) while retaining both strong cytotoxic and antitubulin activities. The introduction of amide (compounds 30-33) and carbamate (compounds 34-37) functionalities at the N1 position of 8 gave analogues with potent antiproliferative activities. The cytotoxic potency of 8 was improved by replacing the carbonyl group with sulfide (compound 41) or oxygen (compound 43), indicating that the carbonyl moiety is important but not essential. The N,N-dimethylamino derivative 13 not only displayed potent cytotoxicity and antitubulin activity, but also showed a markedly improved physicochemical profile relative to the parent compound.

Original languageEnglish
Pages (from-to)1106-1118
Number of pages13
JournalChemMedChem
Volume1
Issue number10
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Oxygen Compounds
Antimitotic Agents
Carbamates
Sulfides
Structure-Activity Relationship
Cytotoxicity
Amides
Substitution reactions
Solubility
Derivatives
Electrons
Pharmaceutical Preparations
compound 30
6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole

Keywords

  • Antitumor agents
  • Indoles
  • Pharmacokinetics
  • Structure-activity Relationships
  • Tubulin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

Cite this

Liou, J. P., Mahindroo, N., Chang, C. W., Guo, F. M., Lee, S. W. H., Tan, U. K., ... Hsieh, H. P. (2006). Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents. ChemMedChem, 1(10), 1106-1118. https://doi.org/10.1002/cmdc.200600125

Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents. / Liou, Jing Ping; Mahindroo, Neeraj; Chang, Chun Wei; Guo, Fu Ming; Lee, Sandy Wen Hsing; Tan, Uan Kang; Yeh, Teng Kuang; Kuo, Ching Chuan; Chang, Yi Wei; Lu, Ping Hsun; Tung, Yen Shih; Lin, Ke Ta; Chang, Jang Yang; Hsieh, Hsing Pang.

In: ChemMedChem, Vol. 1, No. 10, 10.2006, p. 1106-1118.

Research output: Contribution to journalArticle

Liou, JP, Mahindroo, N, Chang, CW, Guo, FM, Lee, SWH, Tan, UK, Yeh, TK, Kuo, CC, Chang, YW, Lu, PH, Tung, YS, Lin, KT, Chang, JY & Hsieh, HP 2006, 'Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents', ChemMedChem, vol. 1, no. 10, pp. 1106-1118. https://doi.org/10.1002/cmdc.200600125
Liou, Jing Ping ; Mahindroo, Neeraj ; Chang, Chun Wei ; Guo, Fu Ming ; Lee, Sandy Wen Hsing ; Tan, Uan Kang ; Yeh, Teng Kuang ; Kuo, Ching Chuan ; Chang, Yi Wei ; Lu, Ping Hsun ; Tung, Yen Shih ; Lin, Ke Ta ; Chang, Jang Yang ; Hsieh, Hsing Pang. / Structure-activity relationship studies of 3-aroylindoles as potent antimitotic agents. In: ChemMedChem. 2006 ; Vol. 1, No. 10. pp. 1106-1118.
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