Antimicrobial, antioxidant and butyrylcholinesterase inhibition activities of extracts and isolated compounds from Scadoxus pseudocaulus and semi-synthetic farrerol derivatives

Abstract

Six known compounds: sideroxylin (1), 5-hydroxylmethyl-2-furancarboxaldehyde (2), C-6,O-7-dimethyldenaromadendrin (3), 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (4), 7-deoxy-transdihydronarciclasine or trans-dihydrolycoricidine (5) and farrerol (6) were isolated from Scadoxus pseudocaulus (Björnstad & Friis) Friis & Nordal (Amaryllidaceae), famous for the treatment of liver cancer, cardiovascular disease, microbial diseases and mental disorders in Western region of Cameroon. The flavanone named farrerol (6) was partially modified by esterification reactions to give six novel semi-synthetic flavanone derivatives named 4′,7-diparamethylbenzoylfarrerol (7), 4′,7-dibutyrylfarrerol (8), 4′-butyrylfarrerol (9), 4′-dodecanoylfarrerol (10), 7-octanoylfarrerol (11) and 4′-octanoylfarrerol (12). Structures of isolated constituents and derivatives were elucidated with the aid of their NMR and MS spectral data as well as with the reported data. The antimicrobial, antioxidant and butyrylcholinesterase inhibition activities of the extracts and their isolated compounds as well as the six novel semi-synthetic flavanone derivatives were evaluated. Ethyl acetate fraction (MIC = 64-512 μg/mL) and compounds 6, 7 and 10 (MIC = 2-16 μg/mL) displayed good antibacterial and antifungal activities that varied among the microbial species. Compound 11 is the most potent antioxidant with IC 50 49.7 μM which is comparable to standard butylated hydroxyanisole having IC 50 value of 44.2 μM. Compounds 12, 4 and 6 also have significant antioxidant activity with IC 50 value 56.5, 59.5 and 58.2 μM, respectively. Compound 7 showed excellent butyrylcholinesterase inhibition activity (IC 50 = 12.6 μM) when compared with standard eserine (IC 50 = 7.8 μM). The overall results of this study indicate that most active samples could be used as complementary medicine after due host toxicity testing.

Antifungal constituents of the plant family Amaryllidaceae

“…As mentioned above, these alkaloids continue to enjoy recognition for their antiproliferative activities (Kornienko & Evidente, ; Nair et al, ). In antifungal activity screenings, the phenanthridone group was represented by narciclasine ( 3 ) and trans ‐dihydrolycoricidine ( 4 ) (Scheme ), which had in common a screen against Cryptococcus neoformans where the former (minimum inhibitory concentration [MIC] 8–16 μg/ml) was shown to be twice as active (Pagning et al, ; Pettit et al, ). Narciclasine was also active against Saccharomyces cerevisiae strains Y166 and TR 1 (MICs 0.2 and >1 mM, respectively; Table ) (Jimenez, Sanchez, & Vazquez, ), whereas trans ‐dihydrolycoricidine exhibited fair growth inhibitory activities against the Candida species Candida albicans and Candida parapsilosis (MICs 0.032 mg/ml, respectively) (Pagning et al, ).…”

“…In antifungal activity screenings, the phenanthridone group was represented by narciclasine ( 3 ) and trans ‐dihydrolycoricidine ( 4 ) (Scheme ), which had in common a screen against Cryptococcus neoformans where the former (minimum inhibitory concentration [MIC] 8–16 μg/ml) was shown to be twice as active (Pagning et al, ; Pettit et al, ). Narciclasine was also active against Saccharomyces cerevisiae strains Y166 and TR 1 (MICs 0.2 and >1 mM, respectively; Table ) (Jimenez, Sanchez, & Vazquez, ), whereas trans ‐dihydrolycoricidine exhibited fair growth inhibitory activities against the Candida species Candida albicans and Candida parapsilosis (MICs 0.032 mg/ml, respectively) (Pagning et al, ). Based on the micromolar activities for both compounds, it can be construed that the C‐1 to C‐10b double bond and C‐7 hydroxyl functionalities are not essential in the antifungal activities of phenanthridone alkaloids.…”

“…Minimum quantity (μg) required for activity; na, not active. Standards: Nystatin MICs 4, 8, and 8 μg/ml against C. albicans , C. parapsilosis , and C. neoformans , respectively (Pagning et al, ); Chlorotrimazole MIC not given against C. albicans (Evidente et al, ); Amphotericin B MIC 0.6 μg/ml against C. albicans (Bonvicini et al, ); Tioconazole MICs 4, 0.03, 0.125, and 0.03 μg/ml against C. albicans , C. dubliniensis , C. glabrata , and L. elongisporus , respectively (Ločárek et al, ); Ketoconazole MIC not given against S. cerevisiae (Castilhos et al, ); Ketoconazole MICs 0.87, 0.92, and 1.26 μg/ml against A. niger , C. albicans , and T. rubrum , respectively (Wu et al, ).…”

“…The nonalkaloid constituents of the Amaryllidaceae which have been studied in fungal culture systems include ceramides ( 32 – 33 ), flavonoid structures ( 34 – 42 ; Scheme ), and a glutamine‐rich peptide (Chu & Ng, ; Pagning et al, ; Wu et al, ). Both Candidamide A ( 32 ) and Candidamide B ( 33 ) were found to be quite active antifungal agents as gauged from a screen against the three pathogens; Aspergillus niger , C. albicans , and Trichophyton rubrum (Wu et al, ).…”

Development and validation of a sensitive UHPLC–MS/MS method for quantitative analysis of farrerol in rat plasma: Application to pharmacokinetic and bioavailability studies

“…[(S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8dimethyl-4-benzopyrone, Figure 1], a 2,3-dihydro-flavonoid isolated from rhododendron, has been shown to have neuroprotective, antiangiogenesis, immunoregulatory, antibacterial, antioxidant and antiinflammatory activities (Dai, Gao, Zhao, Wang, & Xie, 2016;Lai et al, 2016;Pagning et al, 2016;Qin et al, 2015;Qiu et al, 2011;Xiong et al, 2013). Farrerol potently and selectively attenuated IL-6 and IL-8 production by inhibition of PI3K and AKT phosphorylation, resulting in an inhibition of NF-kB activation (Wang, Zhang, & Yu, 2016).…”