AI Summary & Key Takeaways
AI InsightFurther evaluation in intracellular amastigote models is required to determine whether the observed antileishmanial activity is maintained in a host-cell-associated system.
📌 3 Key Takeaways
Abstract
Aims: This study aimed to evaluate the in vitro antileishmanial activity of five quinazolinone derivatives against Leishmania major (L. major) promastigotes and to determine their cytotoxicity toward human umbilical vein endothelial cells (HUVECs) and corresponding selectivity indices (SI). Methods: The quinazolinone derivatives (K1–K5) were tested against logarithmic-phase L. major promastigotes over a concentration range of 3.125–200 µM, with miltefosine used as the reference drug. Antileishmanial activity was assessed after 24 h using the cell viability detection kit-8 (CVDK-8). Cytotoxicity was evaluated in HUVECs, and half-maximal inhibitory concentration (IC50) values were determined by nonlinear regression. SI was calculated as the ratio of the HUVEC IC50 to the L. major IC50. Results: All five quinazolinone derivatives exhibited concentration-dependent antileishmanial activity against L. major, with IC50 values ranging from 29.66 to 41.11 µM. Their HUVEC IC50 values ranged from 69.73 to 91.53 µM. Miltefosine showed greater antileishmanial activity (IC50=21.54 µM) but higher cytotoxicity toward HUVECs (IC50=9.93 µM). Accordingly, K1–K5 showed SI values ranging from 2.15 to 2.38, whereas the SI of miltefosine was 0.46. Conclusion: The five quinazolinone derivatives exhibited in vitro antileishmanial activity against L. major promastigotes and higher SI values than miltefosine under the present experimental conditions. However, the SI values of 2.15–2.38 indicate modest selectivity and should be interpreted cautiously. Further evaluation in intracellular amastigote models is required to determine whether the observed antileishmanial activity is maintained in a host-cell-associated system.