Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II?
Küçük Resim Yok
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Academic Press Inc Elsevier Science
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Discovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I and hTopo II alpha). Biological activity results were found very promising for the future due to two compounds, 5-nitro-2-(4butylphenyl)benzoxazole (1i) and 2-(4-butylphenyl)oxazolo[4,5-b]pyridine (2i), that inhibited hTopo II alpha with 2 mu M IC50 value. These two compounds were also found to be more active than reference drug etoposide. However, 1i and 2i did not show any satisfactory cyctotoxic activity on the HeLa, WiDR, A549, and MCF7 cancer cell lines. Moreover, molecular docking and molecular dynamic simulations studies for the most active compounds were applied in order to understand the mechanism of inhibition activity of hTopo II alpha. In addition, in silico ADME/Tox studies were performed to predict drug-likeness and pharmacokinetic properties of all the tested compounds.
Açıklama
Anahtar Kelimeler
Benzoxazoles, Oxazolo[4,5-B]Pyridines, Topoisomerase I And II Alpha Inhibition, Antitumor, Molecular Docking, Molecular Dynamic Simulation, Dna Topoisomerase-Ii, Drug Discovery, Inhibitors, Prediction, Mechanism, Docking, Cleavage, Cells, Model, Camptothecin
Kaynak
Bioorganic Chemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
112
