新型过渡金属配合物的合成、表征及生物活性研究

为了寻找更好的生物活性化合物,以1-苯基-3-甲基-5-吡唑啉酮和苯甲酰氯为原料,二氧六环为溶剂,回流反应合成了4-酰基吡唑啉酮配体及4种过渡金属配合物,通过元素分析、红外光谱、差热-热重分析、紫外光谱等对其结构进行了表征,表明配合物组成分别为:Cu(L)2、Zn(L)2、Ni(L)2、Mn(L)2;同时利用抑菌圈大小...     

A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis,Characterization, and Biological Studies

The silver(I) N-heterocyclic carbene (NHC) complex bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride ([Ag(EIA)₂]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)₂]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH-SY5Y neuroblastoma cells. The interactions of [Ag(EIA)₂]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)₂]Cl does not react with a few model proteins, but is capable of binding the C-terminal dodecapeptide of thioredoxin reductase hTrxR(488–499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C-terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)₂ complexes.     

Metal Chelates with Some Cellulose Derivatives: V. Synthesis and Characterization of Some Iron(III) Complexes with Cellulose Ethers

Two types of monoligand complexes of FeCl₃, Fe(NO₃)₃ and Fe₂(SO₄)₃ with hydroxyethyl cellulose (HEC) and carboxymethyl cellulose (CMC) were prepared and characterized. Elemental analysis, UV and IR spectro-scopies, conductance and magnetic measurements were used to assign the mode of coordination in the isolated species. The investigation revealed that Fe(III ) exhibits tetrahedral coordination with HEC and CMC. These ligands act as a bidentate chelating agent via the two oxygen atoms of the vicinal hydroxyl and ether groups (ethoxyl or carboxymethyl groups). The prepared complexes have the formula [(HEC) FeCl]Cl, [(HEC) FeNO₃]NO₃, [(HEC)FeSO₄·H₂O]H₂O, [(CMC)FeCl·H₂O]Cl·2H₂O, [(CMC)Fe·2NO₃]3H₂O and [(CMC)-FeSO₄·H₂O]H₂O. The results also showed that the type of cellulose ether (functional group) and the anion of the metal salts used have an effect on the conductivity, structure and absorptivity of Fe(III ) complexes. © of SCI.     

Metal chelates with some cellulose derivatives. Part III. Synthesis and structural chemistry of nickel (II) and copper (II) complexes with carboxymethyl cellulose

Cu(II) and Ni(II) complexes with three grades of carboxymethyl cellulose (CMC) with different degrees of substitution have been synthesized and characterized. Probable structures of the metal complexes are inferred from the electronic and IR spectra, elemental analysis data and magnetic moment measurements. CMC coordinates with cu(II) and Ni(II) via the carboxymethyl and hydroxyl groups. The effect of the degree of substition of the CMC on the mode of chelation is discussed. Ni(II) complexes show an octahedral geometry around the metal ion and exhibit the formula [NiL · 4H₂O]Cl. Cu(II) complexes exist in the square planar form and have the formula Cu(L)₂, where L is uninegatively charged bidentate CMC ligand. The ligand field parameters of Ni(II) complexes are also evaluated.     

Synthesis,Biological Activity and Molecular Docking Studies of Novel Nicotinic Acid Derivatives

In our research, we used nicotinic acid as a starting compound, which was subjected to a series of condensation reactions with appropriate aldehydes. As a result of these reactions, we were able to obtain a series of twelve acylhydrazones, two of which showed promising activity against Gram-positive bacteria (MIC = 1.95–15.62 µg/mL), especially against Staphylococcus epidermidis ATCC 12228 (MIC = 1.95 µg/mL). Moreover, the activity of compound 13 against the Staphylococcus aureus ATCC 43300 strain, i.e., the MRSA strain, was MIC = 7.81 µg/mL. Then, we subjected the entire series of acylhydrazones to a cyclization reaction in the acetic anhydride, thanks to which we were able to obtain twelve new 3-acetyl-2,5-disubstituted-1,3,4-oxadiazoline derivatives. Obtained 1,3,4-oxadiazolines were also tested for antimicrobial activity. The results showed high activity of compound 25 with a 5-nitrofuran substituent, which was active against all tested strains. The most promising activity of this compound was found against Gram-positive bacteria, in particular against Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538 (MIC = 7.81 µg/mL) and ATCC 43300 MRSA strains (MIC = 15.62 µg/mL). Importantly, the best performing compounds did not show cytotoxicity against normal cell lines. It seems practical to use some of these compounds or their derivatives in the future in the prevention and treatment of infections caused by some pathogenic or opportunistic microorganisms.     

Chiral Pool Synthesis,Biological Evaluation and Molecular Docking Studies of C-Furanosidic LpxC Inhibitors

Inhibitors of the bacterial deacetylase LpxC are a promising class of novel antibiotics, being selectively active against Gram-negative bacteria. To improve the biological activity of reported C-furanosidic LpxC inhibitors, the stereochemistry at positions 3 and 4 of the tetrahydrofuran ring was varied. In chiral pool syntheses starting from d -gulono-γ-lactone and d -ribose, a series of (3S,4R)-configured dihydroxytetrahydrofuran derivatives was obtained, of which the (2S,5S)-configured hydroxamic acid 15 ((2S,3S,4R,5S)-N,3,4-trihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (K_i=0.4 μm ), exhibiting the highest antibacterial activity against E. coli BL21 (DE3) and the D22 strain. Additionally, molecular docking studies were performed to rationalize the obtained structure–activity relationships.     

Synthesis,Crystallographic Structure,Theoretical Analysis,Molecular Docking Studies,and Biological Activity Evaluation of Binuclear Ru(II)-1-Naphthylhydrazine Complex

Ruthenium(II)–arene complexes have gained significant research interest due to their possible application in cancer therapy. In this contribution two new complexes are described, namely [{RuCl(η⁶-p-cymene)}₂(μ-Cl)(μ-1-N,N′-naphthyl)]X (X = Cl, 1; PF₆, 2), which were fully characterized by IR, NMR, and elemental microanalysis. Furthermore, the structure of 2 in the solid state was determined by a single crystal X-ray crystallographic study, confirming the composition of the crystals as 2·2MeOH. The Hirshfeld surface analysis was employed for the investigation of interactions that govern the crystal structure of 2·2MeOH. The structural data for 2 out of 2·2MeOH was used for the theoretical analysis of the cationic part [{RuCl(η⁶-p-cymene)}₂(μ-Cl)(μ-1-N,N′-naphthyl)]⁺ (2a) which is common to both 1 and 2. The density functional theory, at B3LYP/6-31+G(d,p) basis set for H, C, N, and Cl atoms and LanL2DZ for Ru ions, was used for the optimization of the 2a structure. The natural bond orbital and quantum theory of atoms in molecules analyses were employed to quantify the intramolecular interactions. The reproduction of experimental IR and NMR spectra proved the applicability of the chosen level of theory. The binding of 1 to bovine serum albumin was examined by spectrofluorimetry and molecular docking, with complementary results obtained. Compound 1 acted as a radical scavenger towards DPPH^• and HO^• radicals, along with high activity towards cancer prostate and colon cell lines.     

Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe,Ru)

The quest to find new inhibitors of biologically relevant targets is considered an important strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC₅₀. Metallocarbonyl derivatives, in general, did not show significant inhibition activity against these enzymes, the most potent inhibitor was the (aminomethyl)benzylphosphonate 8a (IC₅₀ = 1.215 µM against AChE). Molecular docking analysis of AChE and (aminomethyl)benzylphosphonates 8a–c showed the strongest interactions of 8a and AChE compared to isomers 8b and 8c. Cytotoxicity studies of synthesized compounds towards the V79 cell line were also performed and discussed.     

Metal Complexes with Schiff Bases: Data Collection and Recent Studies on Biological Activities

Metal complexes play a crucial role in pharmaceutical sciences owing to their wide and significant activities. Schiff bases (SBs) are multifaceted pharmacophores capable of forming chelating complexes with various metals in different oxidation states. Complexes with SBs are extensively studied for their numerous advantages, including low cost and simple synthetic strategies. They have been reported to possess a variety of biological activities, including antimicrobial, anticancer, antioxidant, antimalarial, analgesic, antiviral, antipyretic, and antidiabetic ones. This review summarizes the most recent studies on the antimicrobial and antiproliferative activities of SBs-metal complexes. Moreover, recent studies regarding mononuclear and binuclear complexes with SBs are described, including antioxidant, antidiabetic, antimalarial, antileishmanial, anti-Alzheimer, and catecholase activities.     

4-酰基吡唑啉酮过渡金属配合物的合成、表征及生物活性研究

为了寻找更好的生物活性化合物,合成了两种4-酰基吡唑啉酮类过渡金属配合物,通过元素分析、红外光谱、差热-热重分析、紫外光谱等对其结构进行了表征,同时对两种细菌和3种真菌进行了生物活性测试。结果表明,在不同浓度梯度下,化合物对细菌都有一定的抑菌性,大部分化合物对真菌有好的抑菌性,特别是对米曲霉菌和白地霉菌的抑制效果最好。     

Design,Synthesis, Biological Evaluation, 2D-QSAR Modeling,and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC₅₀ = 28.23 μg/mL) than ascorbic acid itself which achieved (IC₅₀ = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.     

Synthesis,Molecular Docking and Biological Characterization of Pyrazine Linked 2-Aminobenzamides as New Class I Selective Histone Deacetylase (HDAC) Inhibitors with Anti-Leukemic Activity

Class I histone deacetylases (HDACs) are key regulators of cell proliferation and they are frequently dysregulated in cancer cells. We report here the synthesis of a novel series of class-I selective HDAC inhibitors (HDACi) containing a 2-aminobenzamide moiety as a zinc-binding group connected with a central (piperazin-1-yl)pyrazine or (piperazin-1-yl)pyrimidine moiety. Some of the compounds were additionally substituted with an aromatic capping group. Compounds were tested in vitro against human HDAC1, 2, 3, and 8 enzymes and compared to reference class I HDACi (Entinostat (MS-275), Mocetinostat, CI994 and RGFP-966). The most promising compounds were found to be highly selective against HDAC1, 2 and 3 over the remaining HDAC subtypes from other classes. Molecular docking studies and MD simulations were performed to rationalize the in vitro data and to deduce a complete structure activity relationship (SAR) analysis of this novel series of class-I HDACi. The most potent compounds, including 19f, which blocks HDAC1, HDAC2, and HDAC3, as well as the selective HDAC1/HDAC2 inhibitors 21a and 29b, were selected for further cellular testing against human acute myeloid leukemia (AML) and erythroleukemic cancer (HEL) cells, taking into consideration their low toxicity against human embryonic HEK293 cells. We found that 19f is superior to the clinically tested class-I HDACi Entinostat (MS-275). Thus, 19f is a new and specific HDACi with the potential to eliminate blood cancer cells of various origins.     

对-亚苯基双苯并咪唑过渡金属配合物的合成和荧光性质研究

合成了2,2’-对亚苯基双苯并咪唑的铜、钴、镍配合物,采用元素分析、红外光谱、紫外光谱和摩尔电导率等进行表征,研究了固体荧光性质,发现Ni（II）配合物的荧光发射峰红移了101nm,荧光寿命增加到配体的12倍。     

Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design,Synthesis, Structure–Activity Relationships,Biological Evaluations,and in silico Molecular Docking Studies

To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH₃, OC₂H₅, OC₃H₇) functional groups at C1/C2 of ring A and an acyl (COCH₃ and COPh) or phenylsulfonyl (SO₂Ph and SO₂C₆H₄‐3‐CH₃) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)‐induced antiplatelet aggregation inhibitory activity and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free‐radical‐scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure–activity relationship related to AA‐induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1‐[1,2,9,10‐tetramethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone and 1‐[2‐(benzyloxy)‐1,9,10‐trimethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone to be the best compounds of the series. Moreover, the DPPH free‐radical‐scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10‐tetramethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2‐ethoxy‐1,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 1‐ethoxy‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐1‐propoxy‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, and 1‐(benzyloxy)‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.     

Synthesis,Structure Characterization and Biological Activity of Co (II), Cu (II), and Zn (II) Complexes with (Z)‐3‐((3‐hydroxybenzylidene)amino)pyridin‐1‐ium 4‐(dodecan‐4‐yl)benzenesulfonate Surfactant

(Z)‐3‐((3‐hydroxybenzylidene)amino)pyridin‐1‐ium4‐dodecylbenzenesulfonate anionic surfactant and its cobalt, copper and zinc complexes were synthesized (I, I‐Co, I‐Cu and I‐Zn). The chemical structures of it were characterized by elemental analysis, FTIR, ¹H‐NMR, UV–Vis spectroscopy and atomic adsorption. The effects of the chemical structures of the synthesized anionic surfactant and the type of transition metals on the surface activity are presented in this paper. The thermodynamic parameters show that adsorption and micellization processes are spontaneous. The results of biological activity measurements showed that the synthesized compounds have a great efficiency against gram positive (Bacillus subtilis and Staphylococcus aureus), gram‐ negative bacteria (Pseudomonas aeruginosa and Escherichia coli) and fungi (Candida albicans and Aspergillus niger) as well as the sulfate reducing bacteria (Desulfomonas pigra). The complexation of the anionic surfactant with Co²⁺, Cu²⁺ and Zn²⁺ increase the antimicrobial activity values.