Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies.

2-Arylquinazolines with a range of alkyl polyamines as side chain/ring functional motifs at the 4th-position were considered for antileishmanial study with the rationale that related heterocyclic scaffolds and polyamine functionalities are present in drugs, clinical trial agents, natural products and anti-parasitic/leishmanial agents. Synthesis involves construction of the 2-arylquinazolin-4-one ring and deoxyamination via deoxychlorination followed by S _N Ar-based amination or a methodology of S _N Ar-deoxyamination driven by BOP-mediated hydroxyl-activation. Various alkyl-polyamines important for activities were incorporated. A total of 26 compounds were prepared and screened against Leishmania donovani ( Ld ) promastigote cells using the MTT assay. Most of the investigated series of compounds showed characteristic leishmanicidal properties. Several compounds showed pronounced leishmanicidal activities (IC ₅₀ : 5-6.5 μM) with higher efficiency than the antileishmanial drug miltefosine (IC ₅₀ : 10.5 μM), and relatively less cytotoxicity to macrophage host cells (SI: 9.27-13.5) compared to miltefosine (SI: 3.42). Important pharmacophoric skeletons were identified.
Competing Interests: There are no conflicts to declare.
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