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The Synthesis of 1,3,5‐triazine Derivatives and JNJ7777120 Analogues with Histamine H 4 Receptor Affinity and Their Interaction with PTEN Promoter
Author(s) -
Latacz Gniewomir,
Kechagioglou Petros,
Papi Rigini,
Łażewska Dorota,
Więcek Małgorzata,
Kamińska Katarzyna,
Wencel Przemysław,
Karcz Tadeusz,
Schwed Johannes S.,
Stark Holger,
Kyriakidis Dimitrios A.,
KiećKoowicz Katarzyna
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12752
Subject(s) - pten , chemistry , histamine , promoter , stereochemistry , triazine , gene , microbiology and biotechnology , biochemistry , biology , pharmacology , gene expression , signal transduction , pi3k/akt/mtor pathway , polymer chemistry
The involvement of histamine and H 4 receptor (H 4 R) in cancer has been investigated recently using the H 4 R agonists and antagonists. The scope of the research project was synthesis and exploration of the consequences of a group of compounds with histamine H 4 receptor (H 4 R) affinity on the promoter of PTEN gene encoding the antitumor PTEN protein. The series of novel compounds based either on H 4 R antagonists JNJ 7777120 structure or 1,3,5‐triazine scaffold were synthesized, evaluated for histamine H 4 R affinity and used in this study. Compounds 5 and 7 belonging to the group of JNJ 7777120 analogues showed the highest interaction with the promoter of PTEN gene and weak affinity against H 4 R with K i value >100 μ m . These compounds showed no significant effect on neuroblastoma IMR ‐32 cells viability indicating no correlation between PTEN gene promoter affinity and antitumor activity. Compound 6 , another JNJ 7777120 analogue, showed the highest effect on IMR ‐32 viability with calculated IC 50 = 23.27 μ m . The 1,3,5‐triazine derivatives exhibited generally low or medium interaction with PTEN gene promoter. However, the 1,3,5‐triazine derivative 11 with the para ‐bromo substituent showed the highest affinity against H 4 R with K i value of 520 n m and may be considered as a new lead structure.