Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds
Makaleler > Tam Makale · 2020
Yazarlar: Huseyin Istanbullu, Gülşah BAYRAKTAR, Hasan AKBABA, Ibrahim Cavus, Güneş ÇOBAN, Bilge DEBELEÇ BÜTÜNER, Ali Ahmet Kilimcioglu, Ahmet Ozbilgin, Vildan ALPTÜZÜN, ERÇİN ERCİYAS
ARCHIV DER PHARMAZIE, SCI Expanded İndekslerine Giren Dergi, Uluslararası, 2020, cilt 353
Özet
A series of thiazolopyrimidine derivatives was designed and synthesized as aLeishmania majorpteridine reductase 1 (LmPTR1) enzyme inhibitor. TheirLmPTR1 inhibitor activities were evaluated using the enzyme produced byEscherichia coliin a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro againstLeishmaniasp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compoundL16exhibited an antileishmanial activity for both the promastigote and amastigote forms ofL. tropica, with IC(50)values of 7.5 and 2.69 mu M, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery.