Three-Component Reaction of Diamines with Triethyl Orthoformate and Diethyl Phosphite and Anti-Proliferative and Antiosteoporotic Activities of the Products
Patrycja Petruczynik , Paweł Kafarski , Mateusz Psurski , Joanna Wietrzyk , Zdzisław Kiełbowicz , Jan Kuryszko , Ewa Chmielewska
AbstractA three-component reaction between diamines (diaminobenzenes, diaminocyclohexanes, and piperazines), triethyl orthoformate, and diethyl phosphite was studied in some detail. In the case of 1,3- and 1,4-diamines and piperazines, products of the substitution of two amino moieties—the corresponding tetraphosphonic acids—were obtained. In the cases of 1,2-diaminobenzene, 1,2-diaminocyclohexanes and 1,2-diaminocyclohexenes, only one amino group reacted. This is most likely the result of the formation of hydrogen bonding between the phosphonate oxygen and a hydrogen of the adjacent amino group, which caused a decrease in the reactivity of the amino group. Most of the obtained compounds inhibited the proliferation of RAW 264.7 macrophages, PC-3 human prostate cancer cells, and MCF-7 human breast cancer cells, with 1, trans-7, and 16 showing broad nonspecific activity, which makes these compounds especially interesting in the context of anti-osteolytic treatment and the blocking of interactions and mutual activation of osteoclasts and tumor metastatic cells. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid, which were used as controls. However, studies of sheep with induced osteoporosis carried out with compound trans-7 did not support this assumption.
|Journal series||Molecules, ISSN 1420-3049, (N/A 100 pkt)|
|Publication size in sheets||0.85|
|Keywords in English||bisphosphonic acids, synthesis of C-P bond, multicomponent reactions, P-containing drugs, anti-proliferative activity, osteoclasts, in vivo activity|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 10-05-2021, ArticleFromJournal|
|Publication indicators||= 0; = 0; : 2017 = 1.146; : 2018 = 3.06 (2) - 2018=3.38 (5)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.