Work

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

Year: 2013

Type: article

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 N3-acylated compounds were in general more potent than N1-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.

Source: MedChemComm

DOI: 10.1039/c3md00134b

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

Institutions: Oregon Health & Science University, OHSU Knight Cancer Institute

Language: English

Topic: Quinazolinone synthesis and applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Susan G. Komen, National Institutes of Health, National Institute of General Medical Sciences