Hemi-Synthesis and Anti-Oomycete Activity of Analogues of Isocordoin

Abstract

An efficient synthesis of a series of 4′-oxyalkyl-isocordoin analogues (2–8) is reported for the first time. Their structures were confirmed by 1H-NMR, 13C-NMR, and HRMS. Their anti-oomycete activity was evaluated by mycelium and spores inhibition assay against two selected pathogenic oomycetes strains: Saprolegnia parasitica and Saprolegnia australis. The entire series of isocordoin derivatives (except compound 7) showed high inhibitory activity against these oomycete strains. Among them, compound 2 exhibited strong activity, with minimum inhibitory concentration (MIC) and minimum oomyceticidal concentration (MOC) values of 50 µg/mL and 75 µg/mL, respectively. The results showed that 4′-oxyalkylated analogues of isocordoin could be potential anti-oomycete agents.

Structure-Activity Relationship of Dialkoxychalcones to Combat Fish Pathogen Saprolegnia australis

“…Chalcones, i.e., compounds containing two phenyl rings connected with an alpha-beta unsaturated ketone, have varied and potent biological properties, making them an attractive scaffold for drug discovery [ 10 ]. Specifically, chalcones with O -substitution are of interest, since, to date, only 350 oxyprenylated derivatives have been isolated and/or synthesized, and these compounds possess a wide range of valuable and promising pharmacological activities [ 11 , 12 , 13 ]. In this context, some structure activity relationship studies have suggested that the antimicrobial effect of the synthesized chalcones could be attributable to the presence of a substitution of the chalcone ring system with O -alkyl groups, which is thought to increase their lipophilicity and, consequently, enhance their antimicrobial activity through interaction with cellular membranes [ 14 , 15 ].…”

Isocordoin analogues promote apoptosis in human melanoma cells via Hsp70

“…It has been reported that the lipophilicity of alkyl chains is a key factor in calchone microbial activity and that the inhibition activities decrease as the alkyl chain becomes longer (Ngaini, Fadzillah, & Hussain, ). In addition, our previous research provides evidence that lipophilicity is an important characteristic of anti‐oomycete agents and that oxyalkyl chains on the A‐ring of chalcone contribute to an increase in anti‐oomycete activity (Escobar et al, ). Interestingly, results of the present study are in accord with these previous literature data; in fact, A2058 melanoma cells showed more sensibility to 4‐oxyalkyl‐isocordoin analogues 4 , 5 , and 6 than isocordoin 1 , with the IC 50 values of 12.91 ± 0.031, 24.88 ± 0.013, and 11.62 ± 0.017, respectively (Table ).…”

“…. Recent studies have investigated the introduction of isoprenoids into the structure of chalcones to obtain more active hybrid compounds (Escobar et al, 2017). In this context, the current work aims to study the cytotoxic potential of isocordoin 1 and a series of 4-oxyalkyl-isocordoin analogues 2-8 ( Figure 1) against human melanoma cell line (A2058) and to determine the underlying mechanisms.…”

“…All chemicals were purchased from Sigma-Aldrich Co. (St. Louis, USA), GIBCO BRL Life Technologies (Grand Island, NY, USA), and Santa Cruz Biotechnology (Santa Cruz, CA). Isocordoin 1 and the series of 4oxyalkyl-isocordoin analogues 2-8 were obtained as previously reported (Escobar et al, 2017).…”

“…Isocordoin 1 has been found to have a range of interesting biological properties that may have therapeutic utilities including antioxidant and vasorelaxant effects (Avila‐Villarreal et al, ), as well as a potential anticancer agent in oral‐laryngeal and prostate cancers (Caamal‐Fuentes et al, ; Zhang, Wang, Guo, & Liu, ). Recent studies have investigated the introduction of isoprenoids into the structure of chalcones to obtain more active hybrid compounds (Escobar et al, ). In this context, the current work aims to study the cytotoxic potential of isocordoin 1 and a series of 4‐oxyalkyl‐isocordoin analogues 2 – 8 (Figure ) against human melanoma cell line (A2058) and to determine the underlying mechanisms.…”