Reactivity of 1‐Aryl‐3‐Nitro‐ and 1‐Aryl‐3‐Bromo‐3‐Nitropropenones With Semicarbazides and Benzohydrazide: Convenient Synthesis of Monohydrazones of α‐Diketones

Hydrazone compounds are susceptible to nucleophilic attacks of anions such as fluoride or cyanide due to their tendency toward deprotonation of hydrogen bonded to nitrogen atom in the structure and found applications as ion sensors. In this work, from the condensation reaction of 4-hydroxybenzaldehyde and 2,4-dinitrophenylhydrazine, phenolic hydrazone compound was obtained and the following substitution reaction with 4-nitrobenzenesulfonyl chloride was studied to synthesize a new hydrazone compound with elongated conjugation. Structures of the synthesized compounds were accomplished with 1H NMR, 13C NMR an UV-Vis absorption spectroscopic techniques. According to the spectroscopic data, absorption maximum of the new hydrazone compound was found to shift bathochromically with ca. 120 nm in the presence of nucleophilic fluoride, cyanide, acetate and hydroxide anions.

A Green Chemistry Principle for the Biotransformation of Fungal Biomass Derived Chitosan Into Versatile Nano Scale Materials with High Biocompatibility and Potential Biological Activities—A Review

Copper catalysed conjugate addition is one of the most powerful methods for the creation of the C-C bond as part of the quest to develop new synthetic routes towards the generation of specific chiral centers. In this Ph.D work, our objective was to extend the asymmetric conjugate addition (ACA), to a new class of challenging substrates, the polyconjugated Michael acceptors. The main challenge with this class of substrates is to control the regioselectivity and the enantioselectivity. We discovered that many factors influenced the regioselectivity trends, such as the electronic and the steric properties of the Michael acceptors. Also an important dependence on the nature of the nucleophilic species was observed. By choosing appropriate combination of parameters, we developed various methodologies allowing the selective 1,4- or 1,6-addition with high level of enantiocontrol. We also demonstrated the synthetic value of those methodologies by synthesizing valuable building blocks bearing quaternary stereogenic centers.

Synthesis, characterization and biological assessment of a novel hydrazone as potential anticancer agent and enzyme inhibitor

In order to scientifically search for new sources of secondary metabolites with valuable qualities for phytopharmacognosy, tasks requiring a step-by-step solution were set. The primary task is the development of technologies for obtaining in vitro highly productive biomass of cells of relict gymnosperms of the genus Sequoia, capable of accumulating various classes of secondary metabolites. The study of the accumulation and localization of secondary metabolites allowed us to evaluate the biological activity and cytotoxicity of in vitro Sequoia cultures. In our study, histochemical methods were used to determine the localization of secondary compounds (phenolic and terpenoid in nature) in plant tissues. Secondary metabolites-polyphenols, catechins, and terpenoids-are mainly localized in the epidermal, parenchymal, and conductive tissues of Sequoia leaves and stems. In callus and suspension cultures of Sequoia, secondary metabolites were localized in cell walls and vacuoles. The mineral composition of the nutrient medium (MS and WPM), the light source (photoperiod), and the endogenous content of polyphenols in the primary explant influenced the initiation and growth characteristics of the in vitro culture of Sequoia plants. Inhibition of growth in suspension cultures on the WPM nutrient medium was noted. The cultivation of Sequoia cell lines at a 16 h photoperiod stimulated the formation of polyphenols but had a negative effect on the growth of callus cultures. Extractive substances obtained from intact and callus tissues of evergreen Sequoia demonstrate high biological (fungicidal) activity and cytotoxicity. The inhibitory effect on Fusarium oxisporum was noted when 200 mg/L of Sequoia extract was added to the nutrient medium. Extracts of redwood callus cultures were low in toxicity to normal FetMSC cells but inhibited the growth of lines of "immortal" cervical HeLa cancer cells and human glioblastoma A172. Intact tissues of Sequoia plants and cell cultures initiated from them in vitro are producers of secondary metabolites with high biological activity.

The basic nutrient of all living beings in the developmental age is milk. Milk contains many things necessary for ideal nutrition. One of the enzymes found in bovine milk is lactoperoxidase (LPO; EC 1.11.1.7). The LPO system functions as a natural defense system, especially in newborn babies. Despite the many benefits of milk, contamination of breast milk with environmental toxins is common. Over time, people accumulate a lifetime load of chemicals from drugs to environmental pollutants, and these can be passed on to the baby during breastfeeding. Anthraquinones are colorful compounds that can be produced both naturally and synthetically. These compounds are widely used in industry and medicine due to their biological activities and colorful structures. In this study, in vitro enzyme inhibition study, molecular docking and molecular dynamics (MD) simulation parameters were examined to investigate the inhibitory potential of anthraquinone derivatives, which are widely used as coloring agents, against the lactoperoxidase enzyme. The inhibitors showed competitive inhibition with Ki values between 0.4964 ± 0.042–2.0907 ± 0.1044 µM. 1,2-Dihydroxy-anthraquinone was predicted to have the highest affinity on the LPO receptor, with estimated free binding energies of -7.11 kcal/mol. The stability of both ligand and protein, as shown by the low RMSD and RMSF values, shows that 1,2-dihydroxy-anthraquinone (2) maintains strong and stable interactions throughout the MD simulation, further supporting the high binding affinity and potential biological activity of the compound. We hope that this study will guide the development of drugs targeting the LPO enzyme with anthraquinone derivatives.

At present, the choice of material for mucogingival surgery remains an important issue, as the correct selection improves the effectiveness and stability of postoperative outcomes. Although autogenous grafts are considered the gold standard for gingival recession coverage and soft tissue augmentation, they have several drawbacks: limited availability of donor tissue for covering recession, extensive uncontrolled necrosis in the palatal area including the donor site, patient discomfort, and postoperative complications such as painful wounds on the palate, heavy bleeding, postoperative bone exposure, and recurrent herpetic lesions. Due to these significant disadvantages, xenogenic materials have become widely used. The aim of the study was to conduct a comparative analysis of xenogenic collagen materials for soft tissue augmentation and gingival recession coverage, taking into account their advantages and limitations. Material and methods. A systematic review and analysis of literature sources was conducted using foreign and domestic databases over the past 10 years, including Medline (www.ncbi.nlm.nih.gov), the Russian scientific database eLibrary (https://www.elibrary.ru/), and the Cochrane Library (The Cochrane Central Register of Controlled Trials, CENTRAL, www.thecochranelibrary.com). Results and discussion. The literature analysis demonstrated that xenogenic collagen membranes possess several advantages over non-resorbable membranes and autogenous grafts. Unlike non-resorbable materials, the use of resorbable collagen membranes eliminates the potential risks associated with prolonged presence of foreign material and the need for a second surgery to remove it. Compared with autogenous grafts, collagen-based materials are associated with reduced postoperative pain and discomfort, and they are not limited by the size of the donor site. Resorbable collagen membranes offer high biocompatibility and potential biological activity, as well as sufficient plasticity, simplicity, and convenience in clinical application. Conclusion. Currently, the use of resorbable collagen membranes is becoming increasingly widespread and popular. However, further improvements are needed in their properties, particularly in terms of resorption period and stability when exposed in the oral cavity.

Synthesis and characterization of a zinc-triazole coordination complex with potent antimicrobial and anticancer properties

An efficient and practical method for the synthesis of 1,4-benzodiazepines is reported. This methodology offers a transition-metal-free tandem process in one pot. This process is applicable to the construction of a wide variety of 1,4-benzodiazepines and other tricyclic systems with high potential biological and pharmacological activities.

Hydrazone compounds have interesting biological activities. In this work, a new hydrazone compound 3,5-dihydroxy-N'-(pyridin-2-ylmethylene)benzohydrazide (HL) was synthesized and characterized by IR, UV-Vis, 1H and 13C NMR spectroscopy. The compound reacts with copper chloride and nickel acetate, respectively, to afford metal complexes [CuCl2(HL)]∙CH3OH (1∙CH3OH) and [NiL2]∙2CH3OH∙2H2O (2∙2CH3OH∙2H2O). The complexes were characterized by elemental analysis, and IR and UV-Vis spectroscopy. Structures of HL and the complexes were further confirmed by single crystal X-ray determination. The hydrazone ligand in complex 1 adopts neutral form and coordinates to Cu ion through pyridine nitrogen, imino nitrogen and carbonyl oxygen atoms. The hydrazone ligands in complex 2 adopt monoanionic form and coordinate to Ni ion through pyridine nitrogen, imino nitrogen and enolate oxygen atoms. The Cu atom in complex 1 is in square pyramidal coordination, and the Ni atom in complex 2 is in octahedral coordination. The compounds were tested for their urease inhibitory activities. Complex 1 has remarkable activity on Jack bean urease (IC50 = 0.5 ± 0.1 μmol L-1).

Hydrazone compounds and their derivatives are a kind of special Schiff bases. The multiple hydrazone compounds and their derivatives have a variety of biological activities. This study aims to report the synthesis of diverse hydrazone derivatives and to explore the potent antitumor activities. A series of aromatic heterocyclic sulfonyl hydrazones W1-W15 synthesized from hydrazine or acylhydrazine and aldehydes or ketones were estimated for their in vitro antitumor activities against human cancers. Through the spectral (FT-IR, 1H-NMR, MS) methods, the structure of the compounds was determined. Using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) method, the effects of different concentrations of compounds on growth inhibition and viability of HepG-2 cells were detected. Compound W9 exhibited anti-proliferation activity with IC50 values of 63.91 μmol/L in HepG-2 cell line. In addition, mechanism studies indicated that compound W9 could distinctly prohibit the propagation of HepG-2 cells by arresting the cell cycle at G2/M and inducing apoptosis. Furthermore, we investigated the effectiveness of drug combination treatment with W9 and cis-platinum (cis-DDP) or 5-fluorouracil (5-FU) on HepG-2 cell line. Our results indicated that W9 with synergic treatment of 5-FU or cis-DDP shows better inhibitory cell growth. The combination of the two drugs blocks HepG-2 cells in the G2/M phase. The inhibitory effect of W9 on cell apoptosis was decreased with the increase of drug concentration.

Objective: This study aimed to evaluate the biological activity of benzylidene benzohydrazide derivatives against Cancer Stem Cells (CSCs) through in vitro cytotoxicity tests and silico analyses using molecular docking. Methods: Four hydrazone compounds, namely benzylidene benzo hydrazide (L1), 2-methyl benzylidene benzo hydrazide (L2), 2-nitro benzylidene benzo hydrazide (L3), and 2-bromobenzylidene benzo hydrazide (L4) were used for in silico and in vitro studies. The interaction between hydrazone compounds and the EGFR protein receptor (PDB ID: 1m17) was investigated using the AutoDock tools 1.5.7. The PASS server predicted the biological activities of hydrazone substances. ADMET of hydrazone compounds was assessed using the ADMETLab 2.0. Meanwhile, the cytotoxic activity test of hydrazone compounds on CSCs was evaluated using the MTT Assay method. Results: The results of molecular docking analysis of test compounds L1-L4 provide binding energy values ranging from -6.69 to-7.74 kcal/mol. The binding energy value of L1-L4 is lower than the reference Doxorubicin (-4.30 Kcal/mol). The results of the cytotoxicity test of test compounds with CSCs provide IC50 results for L1 of 0.220±0.360 μg/ml, L2 of 0.034±0.023 μg/ml, L3 of 0.355±0.276 μg/ml, L4 of 1.193±1.122 μg/ml and Doxorubicin of 0.220±0.180 μg/ml. These results indicate that hydrazone derivatives have the potential to be CSCs inhibitor. Conclusion: 2-methyl benzylidene benzo hydrazide (L2) had the potential as a CSCs inhibitor with vigorous cytotoxic activity in vitro against CSCs cell lines

The palladium(II)-catalyzed oxidation of alkenes to carbonyl compounds, usually referred to as the Wacker or Wacker– Tsuji reaction, is arguably one of the best-known reactions catalyzed by palladium. It is an important catalytic process industrially, for the production of ethanal, and synthetically, for the conversion of olefins to ketones. The oxidation of terminal alkenes typically proceeds with selective formation of methylketones. The anti-Markovnikov (AM) Wacker oxidation of terminal olefins to aldehydes remains, however, a major challenge. Under certain conditions, AM selectivity is obtained with styrenes, Michael-type acceptor alkenes and certain olefins, such as 2-vinyl-furanosides, bearing a directing functional group. Indeed, high aldehyde selectivity in the catalytic oxidation of phthalimide-protected allylic amines was reported by our group to yield a key intermediate in the preparation of b-amino acids. On the other hand, Sigman and co-workers have reported the regioselective oxidation of protected allylic amines controlled by various palladium catalysts to yield the corresponding methyl ketones. In 1986, Pd-catalyzed aldehyde selective oxidation of styrene with O2 and CuCl in tBuOH at 30 8C was reported by Feringa. Later, Wenzel reported good selectivity (6:1) for aldehyde formation from allyl acetate (56% combined yield of aldehyde and ketone), in tBuOHwith PdCl2/CH3CN/CuCl/ NaCl at 50 8C. More recently, the aldehyde-selective oxidation of styrenes was reported by Grubbs and co-workers using the catalyst [PdCl2(CH3CN)2], p-benzoquinone as oxidant, and tBuOH as solvent at 85 8C. However, a more general anti-Markovnikov alkene oxidation of non-aryl alkenes under mild conditions remains a challenge, despite the tremendous value in extending this reaction to other substrate classes, in particular allylic alcohols and esters. b-Hydroxy aldehydes are usually prepared by the crossaldol reaction between aldehydes or an aldehyde and a ketone. The direct catalytic formation of an aldehyde by selective attack at the terminal carbon of an a-olefin would be a highly valuable alternative. However, the selective antiMarkovnikov oxidation of allylic alcohols into b-hydroxy aldehydes has proven to be very difficult owing to formation of the ketone products and competing olefin isomerization. Herein, we demonstrate the aldehyde-selective catalytic oxidation of ester-protected allylic alcohols with as low as 0.5 mol% of [PdCl2(PhCN)2] and p-benzoquinone (BQ) as oxidant in tBuOH under ambient conditions. Importantly, the same anti-Markovnikov oxidation products were obtained selectively from both branched and linear allylic esters (Scheme 1), owing to rapid isomerization between allylic esters under the reaction conditions (see below).

Recent research interest in phytochemicals has consistently driven the efforts in the metabolic engineering field toward microbial production of various carotenoids. In spite of systematic studies, the possibility of using C30 carotenoids as biologically functional compounds has not been explored thus far. Here, we generated 13 novel structures of C30 carotenoids and one C35 carotenoid, including acyclic, monocyclic, and bicyclic structures, through directed evolution and combinatorial biosynthesis, in Escherichia coli. Measurement of radical scavenging activity of various C30 carotenoid structures revealed that acyclic C30 carotenoids showed higher radical scavenging activity than did DL-α-tocopherol. We could assume high potential biological activity of the novel structures of C30 carotenoids as well, based on the neuronal differentiation activity observed for the monocyclic C30 carotenoid 4,4′-diapotorulene on rat bone marrow mesenchymal stem cells. Our results demonstrate that a series of structurally novel carotenoids possessing biologically beneficial properties can be synthesized in E. coli.

This thesis deals with the isolation, characterization und chemical derivatization of natural products. Most of the described metabolites show a high potential biological activity which is the result of a complex interaction between the chemical structure of the agent and its molecular target.A very promising source for bioactive natural products is presented by the unexplored area of endophytic fungi. According to a BMBF-research association, the active principles of selected extracts from endophytic fungi could be determined. By this approach 13 partly new secondary metabolites could be isolated, structure elucidated and tested for antibacterial, antifungal, phytotoxic and cytotoxic properties. The absolute configuration of the tetramic acid derivative CJ-21,058, isolated from Phoma sp., could be assigned by a combination of deep temperature NMR-experiments and CD-spectroscopy for the first time. In contrast to other tetramic acids the isolated compound showed an unusual broad spectrum of biological activities. The fermentation of Beauveria sp. exemplified the influence of different cultivation conditions on secondary metabolism. Five Pentaketids, biosynthetically derived from a hypothetical common precursor, could be identified. 7-O-desmethylazamonosporasco! ne from Nodulisporium sp. was isolated for the first time and is produced beside five also new oxygen-analogues of this compound deduced by LC-MS.Chemical degradation of simocyclinone D8, an inhibitor of bacterial gyrase, has been carried out in order to explore structure activity relationships of this modular arranged natural product. For this purpose a selective cleavage of the O-acylic linkage at the sugar moiety D-olivose was established. Application of a methanolic ammonia solution as base led to the desired molecule fragments. The resulting aminocoumarine derivative, which still contains the decatetraene dicarboxylic acid moiety, showed no significant inhibition of gyrase.