Jovana Muškinja

Ferrocenyl based pyrazoline derivatives with vanillic core: synthesis and investigation of their biological properties

Vanillin O-alkylated derivatives and acetylferrocene reacted under Claisen–Schmidt conditions yielding the corresponding ferrocene containing chalcones in good-to-high yields. Under similar conditions, O-alkylated derivatives of acetovanillone were reacted with ferrocenylcarbaldehyde. Two series of novel N-acetyl and N-formyl pyrazoline derivatives were prepared by cyclocondensation of previously described chalcones (containing ferrocene framework and vanillic fragment) with hydrazine hydrate in acidic solvent (formic acid or acetic acid). All synthesized compounds were fully characterized by spectral and physical data and were tested for their biological activity. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration using the broth microdilution method. The activity of the synthesized compounds was compared with standard antibiotics. The most active antibacterial compounds were 1-[5-(3,4-dimethoxyphenyl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone (4a) and 1-[5-(4-benzyloxy-3-methoxyphenyl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl]ethanone (4f); the best antifungal activity was shown by compounds of type 4. The interaction of 4a, 4f, 5a and 5e with DNA and bovine serum albumin (BSA) were investigated by fluorescence spectroscopic method. The results achieved in competitive experiments with ethidium bromide (EB) indicated that 4a and 5e have larger affinity to displace EB from the EB–DNA complex than 4f and 5a, probably through intercalation. Fluorescence spectroscopy data show that the fluorescence quenching of BSA is a result of the formation of the 4a, 4f, 5a and 5e–BSA complex species. Measured values of Ka showed that compounds which contain the acetovanillone-formyl core (5a and 5e) formed more stable complexes with BSA than compounds with the vanillin-acetyl core (4a and 4f), suggesting that 4a– and 4f–BSA are less suitable for drug–cell interactions.

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

O-alkylated vanillin derivatives 2a–f and acetylferrocene 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-3-methoxyphenyl)-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 X-ray 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.

Solvent-free synthesis of novel vanillidene derivatives of Meldrum's acid: biological evaluation, DNA and BSA binding study

A series of novel O-alkyl vanillidene derivatives containing Meldrums acid scaffold under solvent-free conditions were synthesized. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration (MIC) using the broth microdilution. The most active compounds were 5-(4′-hydroxy-2′-iodo-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3a), 5-(4′-acetoxy-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3f), and 5-(4′-bromopropoxy-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3h) with the MIC values ranging from 0.039 to 10 mg mL−1. Antioxidant activity was evaluated by DPPH free radical scavenging activity. 3h showed the largest scavenging activity with an IC50 value of 55.61 μg mL−1 (0.14 mmol L−1). The interaction of 3a and 3h with DNA and bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. The results achieved in competitive experiments with ethidium bromide (EB) indicated that 3a and 3h have an affinity to displace EB from the EB–DNA complex through intercalation. Fluorescence spectroscopy data show that the fluorescence quenching of BSA is a result of the formation of the 3a- and 3h-BSA complex species, and indicate that 3a-BSA is more stable, suggesting that 3h-BSA is less suitable for drug–cell interactions.

Dehydrozingerone analogues: Reaction of O-alkyl derivatives of vanillin and methyl cyclopropyl ketone

O-Alkyl vanillines and methyl cyclopropyl ketone rea cts under ClaisenSchmidt conditions yielding corresponding enone der ivatives, dehydrozingerone analogues with cyclopropane ring fragment, ( E)-1-cyclopropyl-3-(4-alkoxy-3methoxyphenyl)prop-2-en-1-ones. All new compounds w ere well characterized by IR, H and C NMR spectroscopy and physical data.

Cytotoxic and Antimicrobial Activity of Dehydrozingerone based Cyclopropyl Derivatives

A small series of 1‐acetyl‐2‐(4‐alkoxy‐3‐methoxyphenyl)cyclopropanes was prepared, starting from dehydrozingerone (4‐(4‐hydroxy‐3‐methoxyphenyl)‐3‐buten‐2‐one) and its O‐alkyl derivatives. Their microbiological activities toward some strains of bacteria and fungi were tested, as well as their in vitro cytotoxic activity against some cancer cell lines (HeLa, LS174 and A549). All synthesized compounds showed significant antimicrobial activity and expressed cytotoxic activity against tested carcinoma cell lines, but they showed no significant influence on normal cell line (MRC5). Butyl derivative is the most active on HeLa cells (IC50 = 8.63 μm), while benzyl one is active against LS174 and A549 cell lines (IC50 = 10.17 and 12.15 μm, respectively).

4-[(4-Methyl-phen-yl)sulfan-yl]butan-2-one.

In the title compound, C11H14OS, all non-H atoms are essentially coplanar, with a mean deviation of 0.023 Å. In the crystal, centrosymmetrically related molecules are weakly connected into dimers by pairs of C—H⋯O interactions. The dimers are further linked along the a axis by weak C—H⋯π and C—H⋯S interactions.

4-Eth­oxy-3-meth­oxy­benzaldehyde

In the title compound, C10H12O3, all non-H atoms are approximately coplanar, with an r.m.s. deviation of 0.046 Å. In the crystal, very weak C—H⋯O interactions link the molecules into sheets parallel to (101).