Replacement of the methylene of dihydrochalcones with oxygen: synthesis and biological evaluation of 2-phenoxyacetophenones.
With the aim of finding new bioactive compounds, a series of phenoxyacetophenone derivatives 2 were designed and synthesized as oxygen analogs of dihydrochalcones. Also, phenoxyacetophenones were converted to (Z)-oxime derivatives 3 and their geometry were characterized by ¹H-NMR spectroscopy. The in vitro antifungal activity of compounds 2 and 3 was evaluated against Candida albicans, Candida glabrata, Saccharomyces cerevisiae, and Aspergillus niger using micro-dilution method. In general, oxime derivative 3d containing 4-fluorophenoxy moiety showed comparable or more potent antifungal activity (MICs = 15.63-31.25 μg/mL) with respect to the reference drug fluconazole against all tested yeasts. In addition, the antileishmanial activity of title compounds was determined against pormastigote form of Leishmania major. All compounds showed mild growth inhibitory activity against promastigotes. The most active compound was unsubstituted phenoxyacetophenone 2a (IC₅₀ = 80 μg/mL). To anticipate the potential use as drugs, the target compounds were evaluated in their drug-like properties. The in silico values of molecular descriptors for bioactive compounds 2a and 3d revealed that these compounds are within the range set by Lipinski's 'Rule of 5' and show no violation of these rules. Moreover, bioactive compounds 2a and 3d are supposed to be non-mutagenic and non-tumorigenic, with no irritating or reproductive effects.
Department of Chemistry, University of Sistan and Baluchestan, P.O. Box 98135-674, Zahedan, Iran.
Mahsa
M
Ansari
Saeed
S
Emami
Mohammad A
MA
Khalilzadeh
Malek T
MT
Maghsoodlou
Alireza
A
Foroumadi
Mohammad A
MA
Faramarzi
Nasrin
N
Samadi
Sussan K
SK
Ardestani
D000098:Acetophenones / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006801:Humans; D018320:Leishmania major / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000188:drug therapy; D010100:Oxygen / Q000737:chemistry; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*
D000098:Acetophenones; D000935:Antifungal Agents; D047188:Chalcones; D014344:Trypanocidal Agents; C015812:dihydrochalcone; D010100:Oxygen