Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing Hydrazinecarbothioamide or 1,2,4-Triazole Unit

Lungu, Lidia; Ciocârlan, Alexandru; Barba, Alic; Shova, Sergiu; Pogrebnoi, Serghei; Mangalagiu, Ionel I.; Moldoveanu, Costel; Vornicu, Nicoleta; D’Ambrosio, Michele; Babak, Maria V.; Arion, Vladimir B.; Aricu, Aculina

doi:10.1007/s10593-019-02526-1

Cited by 15 publications

(9 citation statements)

References 10 publications

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“…Synthesis and Characterization of HL 1 −HL 3 . The new TSCs HL 1 −HL 3 were obtained by Schiff base condensation r e a c t i o n s of 4 -( 4 -h y d r o x y -3 , 5 -d i m e t h y l p h e n y l)thiosemicarbazide 40 with the corresponding aldehyde (HL 1 , HL 3 ) or ketone (HL 2 ) in boiling ethanol (HL 1 , HL 2 ) or ethanol/water (3:1, HL 3 ) in the absence (HL 1 and HL 2 ) or in the presence of 12 M HCl (HL 3 ). The hydrochloric acid in this latter case was used for Boc-deprotection of the intermediate Boc-HL 3 [Boc-HL 3 +H] + and [Boc-HL 3 −H] − ions) and completed at 85 °C after 7 h, with yields ranging from 67 to 88%.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…2-Formylpyridine, 2-acetylpyridine, and CuCl 2 ·2H 2 O were purchased from commercial suppliers and used without further purification. 3-( tert -Butoxycarbonyl)amino-2-formylpyridine and 4-(4-hydroxy-3,5-dimethylphenyl)thiosemicarbazide were synthesized as reported previously. , KCl, KOH, HCl, and dimethyl sulfoxide (DMSO) were obtained from Reanal. GSH, 2-morpholinoethanesulfonic acid (MES), and 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid (HEPES) were purchased from Sigma-Aldrich and used without further purification.…”

Section: Experimental Sectionmentioning

confidence: 99%

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Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition

et al. 2021

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Three new thiosemicarbazones (TSCs) HL 1 – HL 3 as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of HL 1 – HL 3 with CuCl 2 ·2H 2 O in anoxic methanol afforded three copper(II) complexes, namely, Cu(HL 1 )Cl 2 ( 1 ), [ Cu(L 2 )Cl] ( 2′ ), and Cu(HL 3 )Cl 2 ( 3 ), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as HL 1 – HL 3 at pH 7.4, while being air-sensitive in the basic pH range. In dimethyl sulfoxide they exist as a mixture of E and Z isomers. A mechanism of the E/Z isomerization with an inversion at the nitrogen atom of the Schiff base imine bond is proposed. The monocationic complexes [Cu(L 1 – 3 )] + are the most abundant species in aqueous solutions at pH 7.4. Electrochemical and spectroelectrochemical studies of 1 , 2′ , and 3 confirmed their redox activity in both the cathodic and the anodic region of potentials. The one-electron reduction was identified as metal-centered by electron paramagnetic resonance spectroelectrochemistry. An electrochemical oxidation pointed out the ligand-centered oxidation, while chemical oxidations of HL 1 and HL 2 as well as 1 and 2′ afforded several two-electron and four-electron oxidation products, which were isolated and comprehensively characterized. Complexes 1 and 2′ showed an antiproliferative activity in Colo205 and Colo320 cancer cell lines with half-maximal inhibitory concentration values in the low micromolar concentration range, while 3 with the most closely related ligand to triapine displayed the best selectivity for cancer cells versus normal fibroblast cells (MRC-5). HL 1 and 1 in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Experimental Sectionmentioning

confidence: 99%

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition

et al. 2021

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“…The in vitro antimicrobial activity tests of methanolic extracts from the SR and RW against three species of fungi ( Aspergillus niger , Alternaria alternata, and Penicillium chrysogenum, ATCC 53346, 8741, and 20044) and two species of bacteria ( Pseudomonas aeroginosa and Bacillus sp., ATCC 27813 and 15970) were performed using a previously reported method [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

Chemical Composition and Assessment of Antimicrobial Activity of Lavender Essential Oil and Some By-Products

Ciocârlan

Lupascu

Aricu

et al. 2021

Plants

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The producers of essential oils from the Republic of Moldova care about the quality of their products and at the same time, try to capitalize on the waste from processing. The purpose of the present study was to analyze the chemical composition of lavender (Lavanda angustifolia L.) essential oil and some by-products derived from its production (residual water, residual herbs), as well as to assess their “in vitro” antimicrobial activity. The gas chromatography-mass spectrometry analysis of essential oils produced by seven industrial manufacturers led to the identification of 41 constituents that meant 96.80–99.79% of the total. The main constituents are monoterpenes (84.08–92.55%), followed by sesquiterpenes (3.30–13.45%), and some aliphatic compounds (1.42–3.90%). The high-performance liquid chromatography analysis allowed the quantification of known triterpenes, ursolic, and oleanolic acids, in freshly dried lavender plants and in the residual by-products after hydrodistillation of the essential oil. The lavender essential oil showed good antibacterial activity against Bacillus subtilis, Pseudomonas fluorescens, Xanthomonas campestris, Erwinia carotovora at 300 μg/mL concentration, and Erwinia amylovora, Candida utilis at 150 μg/mL concentration, respectively. Lavender plant material but also the residual water and ethanolic extracts from the solid waste residue showed high antimicrobial activity against Aspergillus niger, Alternaria alternata, Penicillium chrysogenum, Bacillus sp., and Pseudomonas aeroginosa strains, at 0.75–6.0 μg/mL, 0.08–0.125 μg/mL, and 0.05–4.0 μg/mL, respectively.

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“…Chemicals 2,4-Pyridinedicarboxylic acid, 2,4-dihydroxybenzaldehyde, diethyl malonate, t-butyl piperazine-1-carboxylate, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI), 1hydroxybenzotriazole (HOBt), diisopropylethylamine (DIEA), 4,4-dimethyl-3thiosemicarbazide, 4-phenylthiosemicarbazide were purchased from Acros Organics (Fischer Scientific UK; Geel, Belgium), Alfa Aesar (Karlsruhe, Germany), Sigma-Aldrich (Schnelldorf, Germany) and/or Iris-Biotech (Marktredwitz, Germany). N-(4-Hydroxy-3,5-dimethylphenyl)hydrazinecarbothioamide was synthesised in five steps according to published protocols [52].…”

Section: Experimental Partmentioning

confidence: 99%

Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity

et al. 2021

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A series of thiosemicarbazone-coumarin hybrids (HL1-HL3 and H2L4) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely Cu(HL1)Cl2 (1), Cu(HL2)Cl2 (2), Cu(HL3)Cl2 (3) and Cu2(H2L4)Cl4 (4), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D and 2D NMR, IR and UV–vis spectroscopies, cyclic voltammetry (CV) and spectroelectrochemistry (SEC). Re-crystallisation of 1 from methanol afforded single crystals of copper(II) complex with monoanionic ligand Cu(L1)Cl, which could be studied by single crystal X-ray diffraction (SC-XRD). The prepared copper(II) complexes and their metal-free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA-MB-231, sensitive COLO-205 and multidrug resistant COLO-320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC-5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.

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Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing Hydrazinecarbothioamide or 1,2,4-Triazole Unit

Cited by 15 publications

References 10 publications

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition

Chemical Composition and Assessment of Antimicrobial Activity of Lavender Essential Oil and Some By-Products

Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity

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