Leishmaniasis is a parasitic disease with frequent annual incidence. An important issue in chemotherapy is the emergence of resistance, toxicity and lack of cost-effectiveness within current drugs. Therefore, it is of utmost importance to design effective drugs against disease. Current contribution was devoted to the in-silico analysis of binding a few flavonoids/alkaloids to relevant leishmanial targets. Docking scores were used to prioritize acquired affinities and top ranked binders were subjected to subsequent 100-ns MD simulation in explicit water. Binding trajectories revealed the tightest interaction modes for two flavonoid molecules (acerosin and nevadensin) in the uracil DNA glycolase (UDG) active site. Acerosin showed less conformational changes whereas, nevadensin interacted stably during longer simulation time. Conserved interactions of Gln205 and His331 to acerosin indicated their dominant biological role in complex stability. No conserved residues were perceived for nevadensin interactions and a completely new and stable binding conformation could be retrieved after 12 ns simulation. Moreover; acerosin was subjected to DFT analysis for pairwise decomposition evaluations of interacted residues. Although primary mechanisms of action are yet to be discovered, UDG may be a promising target for developing antileishmanial flavonoids.

利什曼病是一种寄生虫病，每年发病率很高。化疗中的一个重要问题是当前药物中出现耐药性、毒性和缺乏成本效益。因此，设计有效的抗病药物显得尤为重要。目前的贡献是专门用于in-silico将一些黄酮类/生物碱与相关利什曼原虫靶标结合的分析。对接分数用于确定获得的亲和力的优先级，并且排名靠前的粘合剂在显性水中进行随后的 100 ns MD 模拟。结合轨迹揭示了尿嘧啶 DNA 乙醇酶 (UDG) 活性位点中两种黄酮类分子（acerosin 和 nevadensin）的最紧密相互作用模式。Acerosin 显示较少的构象变化，而 nevadensin 在较长的模拟时间内稳定地相互作用。Gln205 和 His331 与 acerosin 的保守相互作用表明它们在复合物稳定性中的主要生物学作用。在 12 ns 模拟后，没有发现 Nevadensin 相互作用的保守残基，并且可以恢复全新且稳定的结合构象。而且; acerosin 进行了 DFT 分析，以对相互作用的残基进行成对分解评估。尽管尚未发现主要作用机制，但 UDG 可能是开发抗利什曼类黄酮类化合物的有希望的目标。