Discovery of a potent anti-tumor agent through regioselective mono-N-acylation of 7H-pyrrolo[3,2-f]quinazoline-1,3-diamine

Jingjin Chen, Alina Kassenbrock, Bingbing X. Li, Xiangshu Xiao

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

7H-Pyrrolo[3,2-f]quinazoline-1,3-diamine (1) is a privileged chemical scaffold with significant biological activities. However, the currently accessible chemical space derived from 1 is rather limited. Here we expanded the chemical space related to 1 by developing efficient methods for regioselective monoacylation at N1, N3 and N7, respectively. With this novel methodology, a focused library of mono-N-acylated pyrroloquinazoline-1,3-diamines was prepared and screened for anti-breast cancer activity. The structure-activity relationship (SAR) results showed that N 3-acylated compounds were in general more potent than N 1-acylated compounds while N7-acylation significantly reduced their solubility. Among the compounds evaluated, 7f possessed 8-fold more potent activity than 1 in MDA-MB-468 cells. More importantly, 7f was not toxic to normal human cells. These results suggest that 7f is a novel compound as a potential anti-breast cancer agent without harming normal cells.

Original languageEnglish (US)
Pages (from-to)1275-1282
Number of pages8
JournalMedChemComm
Volume4
Issue number9
DOIs
StatePublished - 2013

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Quinazolines
Acylation
Diamines
Tumors
Breast Neoplasms
Neoplasms
Poisons
Structure-Activity Relationship
Scaffolds (biology)
Bioactivity
Solubility
Libraries
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

Discovery of a potent anti-tumor agent through regioselective mono-N-acylation of 7H-pyrrolo[3,2-f]quinazoline-1,3-diamine. / Chen, Jingjin; Kassenbrock, Alina; Li, Bingbing X.; Xiao, Xiangshu.

In: MedChemComm, Vol. 4, No. 9, 2013, p. 1275-1282.

Research output: Contribution to journalArticle

Chen, Jingjin ; Kassenbrock, Alina ; Li, Bingbing X. ; Xiao, Xiangshu. / Discovery of a potent anti-tumor agent through regioselective mono-N-acylation of 7H-pyrrolo[3,2-f]quinazoline-1,3-diamine. In: MedChemComm. 2013 ; Vol. 4, No. 9. pp. 1275-1282.
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