Premium
Straightforward synthesis, antiproliferative screening, and density functional theory study of some pyrazolylpyrimidine derivatives
Author(s) -
Halim Karema N. M.,
Rizk Sameh A.,
ElHashash Maher A.,
Ramadan Sayed K.
Publication year - 2021
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.4204
Subject(s) - chemistry , pyrazole , nucleophile , electrophile , cytotoxicity , potency , pyrazolone , combinatorial chemistry , pyrimidine , density functional theory , stereochemistry , medicinal chemistry , organic chemistry , computational chemistry , biochemistry , in vitro , catalysis
Tetrahydropyrimidinone derivative was synthesized through one‐pot three components condensation of 1,3‐diphenylpyrazole‐4‐carbaldehyde with pentan‐2,4‐dione and urea under Biginelli reaction conditions. The corresponding chloro‐ and hydrazino derivatives were synthesized and utilized for the construction of some valuable N ‐heterocycles encompassing both pyrazole and pyrimidine cores, such as triazolopyrimidine, tetrazolopyrimidine, pyrazole, and pyrazolone derivatives through condensation with nitrogen nucleophiles and carbon electrophiles. The antiproliferative activity evaluation of the synthesized compounds against four human carcinoma cell lines namely, liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT‐116) cell lines revealed that some of them provided significant potency, as well as the density‐functional theory (DFT) was studied. The permeability of various hydrophilic and hydrophobic synthesized compounds across both normal and cancer cells is confirmed via DFT simulation in which the much higher permeability through aquaporin channels revealed the selective cytotoxicity toward cancer cells.