Ordering selected Zn(II), Cu(II), Pd(II) and Co(III) complex compounds: their separately and combinedly antibacterial therapy and DNA-binding studies

Abstract

In this study, four Co(III)-, Cu(II)-, Zn(II)- and Pd(II)-based potent antibacterial complexes of formula K₃[Co(ox)₃]·3H₂O (I), [Cu(phen)₂Cl]Cl·6.5H₂O (II), [Zn(phen)₃]Cl₂ (III) and [Pd(phen)₂](NO₃)₂ (IV) (where ox is oxalato and phen is 1,10-phenanthroline) were synthesized. They were characterized by elemental analysis, molar conductivity measurements, UV–vis, Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (¹H-NMR) techniques. These metal complexes were ordered in three combination series of I+II, I+II+III and I+II+III+IV. Antibacterial screening for each metal complex and their combinations against Gram-positive and Gram-negative bacteria revealed that all compounds were more potent antibacterial agents against the Gram-negative than those of the Gram-positive bacteria. The four metal complexes showed antibacterial activity in the order I > II > III > IV, and the activity of their combinations followed the order of I+II+III+IV > I+II+III > I+II. The DNA-binding properties of complex (I) and its three combinations were studied using electronic absorption and fluorescence (ethidium bromide displacement assay) spectroscopy. The results obtained indicated that all series interact effectively with calf thymus DNA (CT-DNA). The binding constant (K_b), the number of binding sites (n) and the Stern–Volmer constant (K_sv) were obtained based on the results of fluorescence measurements. The calculated thermodynamic parameters supported that hydrogen bonding and van der Waals forces play a major role in the association of each series of metal complexes with CT-DNA and follow the above-binding affinity order for the series.

Communicated by Ramaswamy H. Sarma     

喙果皂帽花根的化学成分研究

为了解喙果皂帽花(Dasymaschalon rostratum)根的化学成分,采用多种色谱技术从其根的乙醇提取物中分离得到8个化合物。通过波谱数据分析,分别鉴定为:花旗松素(1)、(+)-儿茶素(2)、毛蕊异黄酮(3)、(-)-丁香树脂酚(4)、(-)-皮树脂醇(5)、lirioresinol A(6)、N-反式肉桂酸酰对羟基苯乙胺(7)和羟基酪醇(8)。所有化合物均为首次从该植物中获得。化合物1~8均无明显抗菌活性。     

Calpain inhibitory flavonoids isolated from Orostachys japonicus

The n-butanol (n-BuOH) fraction of Orostachys japonicus A. Berger (Crassulaceae) significantly inhibited calpain activity. Through the activity-guided isolation from the n-BuOH fraction, herbacetin 8-O-α-D-ribopyranoside (1), kaempferol (2), quercetin (3), afzelin (4), astragalin (5), isoquercetin (6) and quercitrin (7) were obtained. Their structures were determined by spectroscopic techniques. Among them, compound 3 and 5 had significant calpain inhibitory activities.     

铁皮石斛内生真菌次生代谢产物研究

为了解铁皮石斛(Dendrobium officinale)内生真菌Phyllosticta aristolochiicola的次生代谢产物,从该真菌中分离得到15个化合物,经波谱分析分别鉴定为N-methyl-2-pyrolidinone (1)、环-(甘氨酸-L-脯氨酸)(2)、环-(D-丙氨酸-L-脯氨酸)(3)、环-(L-缬氨酸-L-脯氨酸)(4)、环-(L-亮氨酸-L-脯氨酸)(5)、cyclo-(L-Leu-D-4-hydroxyprolinyl)(6)、环-(L-苯丙氨酸-L-脯氨酸)(7)、环-(L-苯丙氨酸-L-4-羟基脯氨酸)(8)、环-(L-酪氨酸-L-脯氨酸)(9)、环-(L-苯丙氨酸-L-亮氨酸)(10)、啤酒甾醇(11)、对羟基苯乙醇(12)、对羟基苯乙酸(13)、(2S,3R)-1-(4-羟基苯基)丁烷-2,3-二醇(14)和(2R,3S)-1-苯基丁烷-2,3-二醇(15)。采用MTS法检测抗肿瘤活性表明,化合物2、10和14对HL-60、A-549、SMMC-7721、MCF-7和SW-480细胞株具有一定的抑制活性。     

Stereoselective Synthesis of Some 3-Nitroglucopyranosyladenine Analogues via a Nitroolefin: Intermediate as Potential Therapeutic Agents

Abstract

Three isomers of 9-(4,6-O-benzylidene-3-deoxy-β-D-hexopyranosyl) adenines (2–4) were isolated. The manno isomer 2 could be isomerized to the gluco isomer 3. The manno (2) and galacto isomer (4) were deprotected to 5 and 7, respectively. Michael addition of some organic amines and thiolates to the nitroolefin intermediate (8) gave the corresponding 2-(substituted)-3-nitro-glucopyranosides (9a-h). Compounds 9a,c,h were deprotected to 10a,c,h. Sodium azide with 8 gave the triazolo nucleoside 11, which was deprotected to 12. 2-Deoxy-3-nitro analogue 14 was also obtained.

     

海南产木薯茎化学成分研究

从木薯(Manihot esculenta Crantz)茎的乙醇提取物中分离得到6个化合物,通过波谱分析,分别鉴定为呋喃(1)、肥牛木素(2)、3-吲哚甲酸(3)、3,9,13-megastigmanetriol (4)、穗花杉双黄酮(5)、yucalexin P-21 (6),其中化合物1~5为首次从该植物中分离得到。用滤纸片琼脂扩散法测定了这些化合物的抗菌活性,结果表明化合物1、3、4和6对耐甲氧西林金黄色葡萄球菌(MRSA)和金黄色葡萄球菌均有抑制作用。     

Synthesis and Antiviral Evaluation of Novel 2,3-Dihydroxypropyl Nucleosides from 2- and 4-Thiouracils

Regioselective alkylation of 2-thiouracils 1a–c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-{[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio}pyrimidin-4(1H)-ones 3a–c and 4-{[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio} pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a–c and 9a,b whose deprotection afforded 6a–c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a–c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a–c and 15a,b which were deprotected to give 13a–c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a–c were treated with two equivalents of 2 to give 2,4-bis{[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio}pyrimidines 18a–c. Deprotection of compounds 18a–c gave 2,4-bis[(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.     

Effects of Trialkyltin Chlorides on Escherichia coli Spheroplasts

Valsa ceratosperma, which is the pathogenic fungus of apple canker, was grown in a synthetic medium. The neutral extract from the culture filtrate was chromatographed on a silica gel column to give five isocoumarins. Their structures were determined by MS, UV, IR, ¹H and ¹³C NMR, and CD spectra. Three of them were known compounds; ( ? )-5-methylmellein (1), ( ? )-5-carboxylmellein (2) and ( ? )-5-hydroxylmethylmellein (3). Since the absolute configurations at C-3 in 2 and 3 were not known until now, both were determined to be R by chemical correlations. The two were new compounds; ( + )-(3R,4S)-trans-4-hydroxy-5-methylmellein (4) and ( ? )-(3R,4R)-cis-4-hydroxy-5-methylmellein (5). All the five compounds showed phytotoxicity in a bioassay using detached apple shoots and lettuce seedlings.     

Furanofuran lignans from Vitex negundo seeds

A new furanofuran lignan, vitelignin A (1), together with eight known lignan derivatives, were isolated from the seeds of Vitex negundo. Their structures were identified as (+)-4-oxo-8-hydroxy-2,6-di(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (1), 4-oxosesamin (2), (+)-sesamin (3), (+)-paulownin (4), 4-hydroxysesamin (5), 4,8-dihydroxysesamin (6), 4-oxopaulownin (7), (+)-2-(3-methoxy-4-hydroxyphenyl)-6-(3,4-methylenedioxy)phenyl-3,7-dioxabicyclo[3.3.0]octane (8), and (+)-pinoresinol (9), respectively, based on extensive NMR and MS spectroscopic studies. Compounds 1, 2, and 7 showed moderate antifungal activity in vitro.     

Study of reactivity of cyanoacetohydrazonoethyl-N-ethyl-N-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase

Abstract

This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene 3, 4, 5, 6, coumarin 8, benzocoumarin 9, thiazole 7, piperidine 10, pyrrolidine 11, pyrazole 14 and pyridine 12, 13. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N-methylbenzenesulfonamide (2), which was prepared from condensation of acetophenone derivative 1 with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as in-vitro anti-breast cancer cell line (MCF7) and as in-vitro antimicrobial agents. Compounds 8, 5 and 11 were more active than MTX reference drug and compounds 12, 7, 4, 14, 5 and 8 were highly potent against Klebsiella pneumonia. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification.     

Synthesis of Acyclovir and HBG Analogues Having Nicotinonitrile and Its 2-methyloxy 1,2,3-triazole

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, ¹H, ¹³C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.     

A Convenient Synthesis of Acyclic Adenosines with an Unsaturated Side Chain by Modification of 9-(2,3-O-Isopropylidene-D-Ribityl)Adenine

Abstract

In expectation of discovering their antiviral activity, acyclic adenosine derivatives 7, 11, 12, and 16 were designed as analogs of neplanocin A (NPA) and L-eritadenine which are strong inhibitors of S-adenosyl-L-homocysteine hydrolase. The 1′,5′-seco-analog of 4′-deoxymethyl-NPA (DHCA) 7 was synthesized by dideoxygenation of 9-(2,3-O-isopropylidene-D-ribityl)adenine (2). Acyclic DHCA analogs 11 and 16 were obtained by Wittig reaction of the aldehyde 3 with Ph₃P=CHCO₂Et and Ph₃P=CHCN, respectively. Hydrolysis of the ester 11 afforded a vinylog of L-eritadenine 12. The synthesized acyclic nucleosides 7, 10, and 11 were evaluated for antiviral activity, however, none of them showed any significant antiviral activity.     

毛果鱼藤化学成分及生物活性研究

为了解毛果鱼藤(Derris eriocarpa How)藤茎和根中的生物活性成分,采用柱色谱技术,从其乙酸乙酯萃取部位分离得到6个化合物,分别鉴定为:高丽槐素(1)、美迪紫檀素(2)、大黄素(3)、松脂醇(4)、(6R,9R)9-hydroxy-4-megastigmen-3-one(5)、2-methoxygliricidol(6)。这些化合物均为首次从该植物中分离得到。体外抑菌、细胞毒抑制活性测试结果表明,化合物1、2对部分肿瘤细胞株及结核分枝杆菌(H37Rv)有明显抑制活性。     

Synthesis of Hydantoin Nucleosides with Naphthylmethylene Substituents in the 5-Position

Abstract

(Z)-5-(Naphthylmethylene)-2-thiohydantoin derivatives (3a,b,12a-d) were prepared directly fiom condensations of 2-thiohydantoin derivatives (1,l la,b) with naphthaldehydes. Bisglycosylation took place on reaction of (Z)-5-(naphthylmethylene)- 2-thiohydantoin derivatives (3a,b) with glycosyl halides (4a,b) under alkaline conditions. The bisglycosilated hydantoins produced N₃ glycosylated hydantoins on treatment with ammonia in methanol. (Z)-5-(2-Naphthylmethylene)-2-(benzylidene E-hydrazono)hydantoin (9a) and (Z)-5-(2-naphthylmethylene)-2-(polyhydroxyalkylidene E-hydrazono)hydantoins (9b,c) were prepared fiom the reaction of (Z)-5-(2-naphthyylmethylene)-2- methylmercaptohydantoin (7) with benzylidene E-hydrazone (8a) and monosaccharide E-hydrazones (8b,c). S-Glycosylation also took place when N₃ substituted hydantoins were reacted. The hydantoin nucleosides were tested for their potential activity against HTV and HSV.     

薏苡糠壳的化学成分及其种子萌发活性研究

为了解薏苡(Coix lachryma-jobi)糠壳的化学成分,利用多种柱色谱技术对其乙醇提取物乙酸乙酯萃取部位进行分离,经波谱数据分析鉴定了15个化合物,分别为香豆酸(1)、香豆酸甲酯(2)、2-羟乙基-香豆酸酯(3)、咖啡酸甲酯(4)、阿魏酸甲酯(5)、(E)-3-(4-甲氧基苯基)丙烯酸(6)、2,3-二羟基-...     

Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects

In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by ¹H NMR, ¹³CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1–S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1–S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with K_is in the range of 1.79?±?0.22–2.73?±?0.08?nM against hCA I and in the range of 1.72?±?0.58–11.64?±?5.21?nM against hCA II, respectively.     

Biologically and chemically important hydrazino-containing imidazolines as antioxidant agents

Biologically and chemically useful hydrazinoimidazolines were evaluated as antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH^?), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H₂O₂) scavenging assays, ferric ions reducing power assay, and ex vivo model of rat erythrocytes exposed to 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AAPH) or H₂O₂ were used. The most potent DPPH^? scavengers proved to be hydrazinoimidazolines 3, 2, and 4, revealing excellent antiradical effects – superior or comparable to that of all antioxidant standards used. Moreover, these molecules showed strong NO neutralising potencies – better to that of ascorbic acid (AA) (3), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (3 and 2), butylated hydroxytoluene (BHT) (3 and 2), and butylated hydroxyanisole (BHA) (3, 2, and 4). Compound 4 was also effective in GOR scavenging. The excellent scavenger of GOR, NO, and H₂O₂ proved to be structure 5, with the potency superior or comparable to the majority of antioxidant standards used. In turn, compound 9 was effective in H₂O₂ and GOR neutralisation. All hydrazinoimidazolines revealed the reducing power that is higher than BHT. Moreover, the protective effects of most test compounds on oxidatively stressed erythrocytes were observed. Some structure–activity relationships were disclosed. A significance of the primary hydrazino group on antioxidant effects was confirmed. The most likely DPPH^? and GOR scavenging mechanisms for test compounds were propound. Among all the investigated molecules, hydrazinoimidazolines 5, 3, 2, 4, and 9, due to their excellent or good antiradical activities, can represent promising antioxidant candidates with prospective utility for prevention of diseases related to reactive oxygen/nitrogen species.     

Nucleosides. LIV1 Synthesis and Properties of 3′-Azido- and 2′,3′-Dideoxy-6,7-diphenyllumazine Nucleosides

Abstract

The best approach for the synthesis of1-(3-azido-2,3-dideoxy-β-D-erythro-pento-furanosyl)lumazine (5) and its 6,7-dimethyl- (4) and 6,7-diphenyl derivatives (3) has been found in the interconversion of the corresponding 1-(2-deoxy- β-threo-pentofuranosyl)-lumazines. Monomethoxytritylation at the 5′-position (1 7, 3 4, 4 9) followed by mesylation at the 3′-OH group and subsequent nucleophilic displacement by lithium azide afforded 1 9, 2 9 and 4 7 which were deprotected by acid treatment to give 3–5 in good yields. The syntheses of 1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-6,7-diphenyllumazine (6) and its 6,7-dimethyl derivative (7) were achieved from 1-(2-deoxy-β-D-erythro-pentofuranosyl)-6,7-diphenyllumazine and the corresponding 6,7-dimethyllumazine (2 6) via their 5′-O-p-toluoyl- (2 0, 3 0), and 3′-deoxy-3′-iodo derivatives (2 4, 3 1) to form, after radical dehalogenation and final deprotection, 6 and 7. The newly synthesized lumazine nucleosides have been characterized by elemental analyses, UV-and NMR spectra.     

Synthesis,cyclooxygenase inhibition and anti-inflammatory evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing methanesulphonyl pharmacophore

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives 13a–p were synthesized via aldol condensation of 3/4-nitroacetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-methanesulfonylphenylhydrazine hydrochloride. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All compounds were more potent inhibitors for COX-2 than COX-1. While most compounds showed good anti-inflammatory activity, compounds 13d, 13f, 13k and 13o were the most potent derivatives (ED₅₀?=?66.5, 73.4, 79.8 and 70.5?μmol/kg, respectively) in comparison with celecoxib (ED₅₀?=?68.1?μmol/kg). Compounds 13d, 13f, 13k and 13o (ulcer index?=?3.89, 4.86, 4.96 and 3.92, respectively) were 4–6 folds less ulcerogenic than aspirin (ulcer index?=?22.75) and showed approximately ulceration effect similar to celecoxib (ulcer index?=?3.35). In addition, molecular docking studies were performed for compounds 13d, 13f, 13k and 13o inside COX-2 active site which showed acceptable binding interactions (affinity in kcal/mol ?2.1774, ?6.9498) in comparison with celecoxib (affinity in kcal/mol ?6.5330).     

Synthesis,Antitumor, and DNA Binding Behavior of Novel 4-(2-Hydroxyquinolin-3-yl)-6-Phenyl-5, 6 Dihydropyrimidin Derivatives in Aqueous Medium

This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a–f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a–f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, ¹HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evulated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) observed 4.3 × 10⁵ M^?1 for (2a), and 3.8 × 10⁵ M^?1 for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).