Abstract
A pyrrolo[1,2-a]pyrazine-based chemical territory was expanded via construction of new chemical library with distinctive substitution patterns, which was made possible by regiodivergent electrophilic acylation followed by aldol condensation. Biological screening of the compounds in this class revealed that the viability of human lymphoma U937 cells was strongly inhibited by 6b with a methoxy group at the o-position of the aromatic ring, but not by compounds 6t-w bearing a halogen at the o-position. Furthermore, 6x having a 2,4-dimethoxyphenyl group inhibited the survival of U937 cells more potently than 6b. In contrast, 6y possessing a 2,5-dimethoxyphenyl moiety did not show effective inhibition, implying the importance of orientation of the substituent(s) around the benzene ring. The anticancer action of 6x with safe therapeutic window could be associated with the FTase-p38 signaling axis.
Original language | English |
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Pages (from-to) | 1350-1356 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 29 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2019 Jun 1 |
Bibliographical note
Funding Information:We thank the National Research Foundation of Korea (NRF-2017R1A2A2A05069364, NRF-2018R1A6A1A03023718, 2015M3A9B6027818, and 2016K2A9A1A03904900) for generous financial support. MP and SHK were supported by project grants from Korea Research Institute of Chemical Technology (KK1703-F02, KK1803-F00, and KK1932-20). We specially thank Prof. Nam Sook Kang (Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea) for supporting cheminformatics and molecular docking simulation studies.
Funding Information:
We thank the National Research Foundation of Korea (NRF-2017R1A2A2A05069364, NRF-2018R1A6A1A03023718, 2015M3A9B6027818 , and 2016K2A9A1A03904900 ) for generous financial support. MP and SHK were supported by project grants from Korea Research Institute of Chemical Technology ( KK1703-F02 , KK1803-F00 , and KK1932-20 ). We specially thank Prof. Nam Sook Kang ( Graduate School of New Drug Discovery and Development, Chungnam National University , Daejeon, Republic of Korea) for supporting cheminformatics and molecular docking simulation studies.
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry