Preliminary antifungal activity assay of selected chlorine‐containing derivatives of xanthone and phenoxyethyl amines

Abstract

The aim of this study was to evaluate antifungal activity in a diverse group of chlorine-containing xanthone and phenoxyethyl amine derivatives - and to select the most promising compounds for further studies. The antifungal efficacy of 16 compounds was tested with qualitative and quantitative methods against both reference and clinical strains of dermatophytes, moulds and yeasts. The disc-diffusion method has demonstrated that from 16 tested compounds, 7 possess good antifungal activity against dermatophytes and/or moulds while none of them has shown good efficacy against yeasts or bacterial strains. The most active compounds (2, 4, 10, 11, 12, 15, 16) were tested quantitatively by broth dilution method to obtain MIC values. The MIC values against dermatophytes ranged from 8 to 64 μg/ml. Compound 2 was the most active one against dermatophytes (MIC and MIC were 8 μg/ml). The MIC values for moulds ranged from 16 to 256 μg/ml. Compound 4 was the most active one against moulds, with MIC and MIC values amounting to 32 μg/ml. Among the tested compounds, compound 4 (derivative of xanthone) was the most active one and expressed good antifungal efficacy against clinical strains of dermatophytes and moulds. However, another xanthone derivative (compound 2) was the most active and selective against dermatophytes.

Design, synthesis and activity against Staphylococcus epidermidis of 5‐chloro‐2‐ or 5‐chloro‐4‐methyl‐9H‐xanthen‐9‐one and some of its derivatives

“…So far, some significant activity against the bacteria Helicobacter pylori has been found (Klesiewicz et al, 2016). We noticed interesting influence in antibacterial activity of chlorine substituent in xanthone derivatives in positions 6 or 7 as well as in 4-chlorophenoxyalkylamines (Klesiewicz et al, 2018); therefore, the substituent remains interesting for us when attempting drug design for new antibacterial compounds. This time we aimed to try a new position-C5.…”

“…The xanthone moiety (9H-xanthen-9-one, dibenzo-γ-pyrone) is a naturally occurring heterocyclic structure, present in medicinal plants such as Garcinia mangostana (α-mangostin, Figure 1; Dharmaratne et al, 2013;Jung et al, 2006), Mangifera indica (Pinto et al, 2005) and Cudrania cochinchinensis (Fukai et al, 2005). Therefore, there have been many attempts to search for biological activity within the group of derivatives of xanthone, where significant biological activities have been found, such as: anticancer (Szkaradek et al, 2016), anticonvulsant (Szkaradek et al, 2013;Waszkielewicz et al, 2013), antioxidant (Jung et al, 2006), antifungal (Klesiewicz et al, 2018) and antimicrobial (Fukai et al, 2005)-some amount of research has been performed by our team.…”

Synthetic Chiral Derivatives of Xanthones: Biological Activities and Enantioselectivity Studies

“…Marona et col. [163,164,165,166,167,168,169] also described the synthesis and biological activity evaluation of a series of aminoalkanolic CDXs 180 – 205 , 217 – 220 , 238 (Figure 18, Figure 19 and Figure 20). More recently, they synthesized the aminoalkanolic CDXs 206 – 243 (Figure 18, Figure 19 and Figure 20), being tested for anticonvulsant, antimicrobial and cardiovascular activities [170,171,172,173,174]. CDXs 180 – 194 , 198 – 202 were synthesized by condensation of an appropriate 2-bromomethylxanthone or 2-bromomethyl-7-chloroxanthone with the adequate aminoalkanol in toluene, in the presence of anhydrous potassium carbonate [163,164,175].…”

“…The exchange of secondary amino group of compound 189 for a tertiary amino group (compound 193 ) was generated by reductive N -methylation [163]. Compound 210 , however, was synthesized through the chlorination of compound 186 with thionyl chloride in toluene [170].…”

“…In recent years, several aminoalkanolic CDXs 210, 228 – 230, 241 – 242 have been evaluated for their antibacterial and antifungal activities [170,172]. Compound 210 was evaluated against several dermatophytes, moulds and yeasts, exhibiting good activity results against ten strains of the Aspergillus fumigatus, niger and flavus moulds, being among the tested compounds the most active [170]. This CDX also exhibited moderate to good activity against some strains of the Trichophyton mentagrophytes and rubum dermatophytes, while being inactive against the Candida albicans yeast [170].…”