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Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies.
- Source :
-
RSC medicinal chemistry [RSC Med Chem] 2022 Jan 06; Vol. 13 (3), pp. 320-326. Date of Electronic Publication: 2022 Jan 06 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- 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 <subscript>N</subscript> Ar-based amination or a methodology of S <subscript>N</subscript> 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 <subscript>50</subscript> : 5-6.5 μM) with higher efficiency than the antileishmanial drug miltefosine (IC <subscript>50</subscript> : 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.<br />Competing Interests: There are no conflicts to declare.<br /> (This journal is © The Royal Society of Chemistry.)
Details
- Language :
- English
- ISSN :
- 2632-8682
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- RSC medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 35434631
- Full Text :
- https://doi.org/10.1039/d1md00336d