Ferrocenyl chalcones with O-alkylated vanillins: synthesis, spectral characterization, microbiological evaluation, and single-crystal X-ray analysis

Abstract

O-alkylated vanillin derivatives 2a-f and acetyl ferrocene react under Claisen-Schmidt conditions, resulting in good-to-high yields of the corresponding ferrocene chalcones 3a-f. None of the resultant compounds 3b-f has been previously described in the literature. All synthesized compounds were characterized by spectral and physical data, whereas two of them, 1-ferrocenyl-3-(4-ethoxy-3methoxyphenyl)-prop-2-en-1-one (3b) and 1-ferrocenyl-3-(4-buthoxy-3-methoxy-phenyl)-prop-2-en-1-one (3e), were crystalline substances, suitable for single-crystal Xray analysis, which confirmed undoubtedly their structures.Chalcones 3a-f were tested for their biological activity and demonstrated relatively good in vitro antimicrobial activity towards different strains of bacteria and fungi. The best antibacterial activity is expressed by compounds 3b and 3c, while compound 3d shows the best antifungal activity.

Synthesis and DFT Calculations of Novel Vanillin-Chalcones and Their 3-Aryl-5-(4-(2-(dimethylamino)-ethoxy)-3-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde Derivatives as Antifungal Agents

“…Compound 4a showed the lowest MFC values against the three dermatophytes (31.25 µg/mL). In previous works Muškinja [ 10 ], Burmudžija [ 20 ], Patel [ 34 ] synthetized a series of chalcones and pyrazoline derivatives containing the vanillin moiety and tested them against several fungi including C. albicans and A. niger all of them showing negligible activity (MICs ≥ 625 µg/mL). Although the chalcone or pyrazoline derivatives reported by them differ from the series presented here in the substitution of the vanillin OH or in the ring A, the previous and presently reported compounds share the structural characteristics that they are both chalcones or pyrazolines and both possess the vanillin moiety as the B-ring, so our results add new important data to the activity of chalcone and pyrazoline vanillin derivatives possessing a vanillin moiety as ring B, corroborating that they are not good inhibitors of C. albicans , or Aspergillus spp., but adding an important finding that is their promising activity against dermatophytes and C. neoformans .…”

“…The chalcone and pyrazoline moieties are important classes of compounds widely used as key building blocks for biologically active compounds and they are considered promising candidates for antifungal drugs. Chalcones have been extensively studied for their broad spectrum of activities as anti-inflammatory [ 7 ], antifungal [ 8 , 9 ], antibacterial [ 10 ], antioxidant [ 11 ], antimalarial [ 12 , 13 ] and antitumor [ 14 , 15 ] agents. One of our previous studies demonstrated that the mode of antifungal action of certain chalcones is related to the inhibition of the synthesis of the fungal cell-wall polymers such as (1,3)β- d -glucan synthase.…”

“…Previous studies have also shown that the use of vanillin compounds as starting materials in organic synthesis led to the formation of several vanillin-derivatives with a wide spectrum of biological activities [ 10 , 25 , 26 , 27 ].…”

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives

“…In these experiments, antibacterial effect was observed against the both Gram ‐positive and Gram ‐negative bacteria but it should be noted that the Gram ‐negative bacteria were more resilient. It has been generally reported that the Gram ‐negative bacteria are more resistant than Gram ‐positive . This resistance is likely, due to the fact that Gram ‐negative bacteria have a wall which itself is surrounded by an outer complex membrane, slowing down the passage of hydrophobic compounds.…”

Sonochemical Synthesis of 2’-Hydroxy-Chalcone Derivatives with Potential Anti-Oomycete Activity

“…Chalcones are well documented as biologically active natural products [ 13 ], with potential use in diseases caused by Phytophthora spp. In this context, several studies have shown that natural and synthetic chalcones with –OH and – O- alkyl chains linked to different positions of the A and B rings are known to have bactericidal, antifungal, anthelmintic, antiviral, and anti-oomycetes activities [ 14 , 15 , 16 , 17 , 18 ]. These reports illustrate that antimicrobial activity depends on the number, type, and length of side chain, and position of these substituents in the aromatic ring.…”