Open AccessBenzophenone Derivatives Showed Dual Anti-Inflammatory and Antiproliferative Activities by Inhibiting COX Enzymes and Promote Cyclin E Downregulation
Author(s) -
Laís R. S. Folquitto,
Thiago Alves de Souza,
Jaqueline Pereira Januário,
Isadora Nascimento,
Brenda Brandão,
Maria Cláudia Rodrigues Moreira,
Renato de Oliveira Horvath,
Marcelo dos Santos,
Luiz Felipe Leomil Coelho,
Márcia Paranho Veloso,
Marisi G. Soares,
Diogo Teixeira Carvalho,
Marisa Ionta,
Daniela Aparecida ChagasPaula,
Danielle Ferreira Dias
Publication year - 2022
Publication title -
journal of the brazilian chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.337
H-Index - 70
eISSN - 1678-4790
pISSN - 0103-5053
DOI - 10.21577/0103-5053.20210154
Subject(s) - chemistry , in vivo , population , cell cycle checkpoint , cell cycle , docking (animal) , pharmacology , cell culture , cancer research , cell , biochemistry , biology , medicine , genetics , microbiology and biotechnology , environmental health , nursing
Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo antiinflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7) showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA‑MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.