由于缺乏疫苗，利什曼病的治疗主要依靠化疗。然而，现有药物的低功效、寄生虫抗性和毒性使得有必要开发有效且更安全的疗法。 Fuchino 等人。报道了一系列苯并[c]菲啶对大利什曼原鞭毛体具有潜在的杀利什曼活性。为了推动这些化合物的药物开发，了解它们的分子靶点、作用机制、结合相互作用和结构要求至关重要。在这项研究中，对 30 种苯并[c]菲啶进行了分子对接、网络药理学、2D-QSAR 和 3D-QSAR CoMFA 研究。对接分析表明，与其他靶标相比，所有分子对 L. Major 核苷二磷酸激酶 (NDPK) 都具有很强的结合亲和力。 10-异丙氧基血根碱具有最高的结合亲和力（-10.6kcal/mol）并形成离子和疏水相互作用。对最活跃化合物的网络药理学分析确定丝氨酸/苏氨酸蛋白激酶 Mtor 是苯并[c]菲啶类药物在人类中的潜在抗利什曼病靶标。所有对接化合物的高亲和力分数> -7.0kcal/mol 都证实了这一点。 GO 和 KEGG 通路富集鉴定 Reg.脂肪酸氧化 (BP)、TORC1 复合物 (CC)、RNA 聚合酶 III 1 型启动子序列特异性 DNA 结合 (MF) 和急性髓系白血病（KEGG 途径）的中心基因高度富集。 2D和3D-QSAR CoMFA模型均满足以下内部和外部验证测试：2D-QSAR：R2Train = 0.9040，Q2cv = 0.8648，R2adj = 0.8838，R2Test = 0.8740； 3D-QSAR：r2 = 0.998，q2 = 0.526，SDEP = 0.856。这些分子实际上可以被评价为优良的抗利什曼病药物。

Leishmaniasis treatment primarily relies on chemotherapy due to lack of vaccines. However, the low efficacy, parasite resistance, and toxicity associated with existing drugs necessitate the development of effective and safer therapies. Fuchino et al. reported promising leishmanicidal activity in a series of benzo[c]phenanthridines against L. major promastigotes. To progress these compounds towards drug development, it is crucial to understand their molecular targets, mechanisms of action, binding interactions, and structural requirements. In this research, molecular docking, network pharmacology, 2D-QSAR, and 3D-QSAR CoMFA studies were performed on 30 benzo[c]phenanthridines. Docking analysis showed that all molecules had a strong binding affinity to L. major-nucleoside diphosphate kinase (NDPK) compared to the other targets. 10-isopropoxy sanguinarine had the highest binding affinity (-10.6 kcal/mol) and formed ionic and hydrophobic interactions. Network pharmacology analysis of the most active compounds identified serine/threonine-protein kinase Mtor as a potential antileishmaniasis target in humans for benzo[c]phenanthridines. This was confirmed with high-affinity scores > -7.0 kcal/mol for all the compounds docked. GO and KEGG pathway enrichment identified Reg. of fatty acid oxidation (BP), TORC1 complex (CC), RNA polymerase III type 1 promoter sequence-specific DNA binding (MF), and Acute myeloid leukemia (KEGG pathway) to be highly enriched with the hub genes. Both 2D and 3D-QSAR CoMFA models satisfied the internal and external validation tests as follows: 2D-QSAR: R2Train = 0.9040, Q2cv = 0.8648, R2adj = 0.8838, and R2Test = 0.8740; and 3D-QSAR: r2 = 0.998, q2 = 0.526, and SDEP = 0.856. The molecules can be practically evaluated as superior antileishmaniasis agents.