Synthesis and antiviral bioactivity of novel chalcone derivatives containing purine moiety

A series of novel chalcone derivatives containing purine group was synthesized and evaluated for their antiviral activities against cucumber mosaic virus and tobacco mosaic virus. Compound 3o exhibited remarkable antiviral activities and strong combining capacity to tobacco mosaic virus coat protein.     

Synthesis,antiviral activity,and 3D-QSAR study of novel chalcone derivatives containing malonate and pyridine moieties

Several novel chalcone derivatives containing malonate and pyridine moieties were synthesized, and their structures were confirmed by ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, ¹⁹F nuclear magnetic resonance, infrared, and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against cucumber mosaic virus (CMV) at 500 μg/mL. In particular, compounds 5l and 5n showed significant curative activities against CMV in vivo with 50% effective concentration (EC₅₀) values of 186.2 and 211.5 μg/mL, respectively; these values are even better than that of ningnanmycin (330.5 μg/mL). A 3D quantitative structure–activity relationship study was carried out using the comparative molecular field analysis technique based on curative activities against CMV. Results revealed good predictive ability with cross-validated q² and non-cross-validated r² values of 0.517 and 0.990, respectively.     

Design,synthesis and antiviral activities of chalcone derivatives containing pyrimidine

A series of chalcone derivatives (T1-T23) containing pyrimidine were synthesized, characterized, and assessed for their antiviral activity against tobacco mosaic virus (TMV) activities. Most target compounds displayed better antiviral activities against TMV than commercial ningnanmycin. Among them, the EC₅₀ value of curative activities of compounds T1, T7, T9 and T19 (219.2, 228.2, 279.9 and 234.9 μg/mL, respectively) were superior to that of ningnanmycin (320.1 μg/mL). In addtion, the EC₅₀ value of protective activities of compounds T5, T9, T19 and T23 (235.0, 220.0, 199.5 and 187.2 μg/mL, respectively) were superior to that of ningnanmycin (307.4 μg/mL). Then, the antiviral mechanism of T19 and TMV coat protein (TMV-CP) was preliminarily investigated by microscale thermophoresis (MST) and molecular docking technology. The results showed that T19 had a strong binding affinity for TMV coat protein, and its dissociation constant (K_d) was 0.00310 ± 0.000916 μM, which was superior to ningnanmycin(0.165 ± 0.0799 μM). This study suggests that chalcone derivatives containing pyrimidine could be used as novel antiviral agents for controlling the plant viruses.     

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/mL, which was superior to ningnanmycin (409.3 mg/mL).     

Asymmetric synthesis and antiviral activity of novel chiral amino-pyrimidine derivatives

By using a chiral cinchona alkaloid-squaramide catalyst, a series of both enantiomers of novel amino-pyrimidine derivatives can be obtained in an enantioselective three-component one-pot Mannich reaction with high yields and excellent enantioselectivities. In addition, these chiral derivatives were found to exhibit higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial agent ningnanmycin. In particular, chiral compounds (R)-4b and (R)-4e showed excellent antiviral activity against TMV at a concentration of 500?μg/mL, with a curative activity of 56.8% and 55.2%, respectively, a protection activity of 69.1% and 67.1%, respectively, and an inactivation activity of 91.5% and 94.3%, respectively. These values are superior to those of the agent ningnanmycin (which has curative, protective, and inactivation activities of 52.9%, 62.8%, and 90.4%, respectively). The antiviral mechanisms and enhanced antiviral activities of these chiral derivatives are interesting subjects for future investigation.     

Synthesis and bioactivity of novel strobilurin derivatives containing the pyrrolidine-2,4-dione moiety简

（E）-Methyl-2-（2-（bromomethyl）phenyl）-3-methoxyacrylate was reacted with substituted 1-acetylpyr-rolidine-2,4-diones and 3-（1-（hydroxylamino）ethylidene）pyrrolidine-2,4-diones respectively to synthesize two series of/%methoxyacrylate derivatives containing the pyrrolidine-2,4-dione moiety. The structures of the targeted compounds were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. The fungicidal activity against Rhizoctonia solani, Botrytis cinerea and Fusarium graminearum was evaluated. The bioassay results demonstrated that these compounds showed visible fungicidal activity.     

含N-取代哌嗪片段的查尔酮衍生物的合成及其细胞毒活性

以4-甲氧基苯甲醛与2-溴-4’-氟苯乙酮为原料,经缩合、取代反应后,再与α-溴代酮或α-溴代酯反应,合成得到8个查尔酮哌嗪衍生物(3a~3h),其结构经1H NMR、13C NMR和HRMS确证。采用MTT法初步测试了所合成化合物的体外细胞毒活性,结果表明,哌嗪环上含酮基取代的化合物对肿瘤细胞株A549和SGC7901均表现出良好的抑制活性,特别是化合物3a(IC50=0.28μmol/L,2.53μmol/L)活性最高,值得进一步深入研究。     

Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety

Abstract

A series of novel 1,2,4-triazole derivatives containing a pyrimidine moiety were synthesized and their fungicidal activities were evaluated. The preliminary biological test indicated that some of the target compounds exhibited moderate to good fungicidal activities against the tested plant pathogenic fungi compared with the commercial agent. Among them, compounds 9n and 9o exhibited excellent antifungal activity against Phompsis sp., with the half-maximal effective concentration (EC₅₀) values of 25.4 and 31.6?μg/mL, which were even better than the commercial agent of Pyrimethanil (32.1?μg/mL). Meanwhile, compound 9o showed better fungicidal activities against B. dothidea and B. cinerea with 40.1 and 55.1?μg/mL, respectively, in comparison with that of commercial Pyrimethanil (57.6 and 62.8?μg/mL).     

Improved and rapid synthesis of new coumarinyl chalcone derivatives and their antiviral activity

Two closely structurally related coumarins, 4-hydroxy-8-isopropyl-5-methylcoumarin and 4-hydroxy-6-chloro-7-methylcoumarin were acylated at C-3 and further converted to the respective chalcones and two series of eighteen new compounds, which were evaluated for possible antiviral activity.     

Synthetic derivatives of spiromesifen and their bioactivity research

Sixteen new derivatives of spiromesifen were synthesized from 3-(2,4,6-trimethylphenyl)-4-hydroxy-△~3-dihydrofuran-2-one. Their bioactivities against diamondbackmoth(Plutella xybstella) and spider mites(Tetranychus cinnabarinus) were also evaluated. The structures of these derivatives were confirmed by ~1H NMR,MS.     

Design,synthesis, and bioactivity evaluation of novel thiochromanone derivatives containing an oxime or oxime ether moiety

In this study, using botanical active component thiochromanone as the lead compound, a series of novel thiochromanone derivatives containing an oxime or oxime ether moiety were designed and synthesized. The half-maximal effective concentration (EC₅₀) values of compound 4a against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were 6, 10, and 15 μg/ml, respectively, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, compound 4a also revealed better antifungal activity against Botrytis cinerea, with the EC₅₀ value of 18 μg/ml, than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing an oxime or oxime ether moiety.     

Synthesis and bioactivity evaluation of some novel sulfonamide derivatives

A simple and convenient method for the synthesis of biologically active sulfonamide derivatives was achieved. All the title compounds were characterized by spectral and elemental analysis. They were further screened in vitro for their abilities towards antibacterial, antifungal and antioxidant activities. The compound N,N'-(3,3′-dimethoxybiphenyl-4,4′-diyl)bis(4-fluorobenzenesulfonamide) (5b) and N-(3-(9H-carbazol-4-yloxy)-2-hydroxypropyl)-4-fluoro-N-isopropylbenzenesulfonamide (5e) exhibited good activity when compared to the standard bactericide, Chloramphenicol and fungicide, Ketoconazole respectively. The compounds (2S)-N-((2S,4S)-5-(4-Chloro-phenylsulfonamido)-4-hydroxy-1, 6-diphenylhexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrim-idin-1(2H)-yl)butan-amide (4f) and (2S)-N-((2S,4S)-5-(4-fluorophenylsulfonamido)-4-hydroxy-1,6-diphenyl-hexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)bu-tana-mide (5f) exhibited good antioxidant activity when compared with standard antioxidant, Ascorbic acid.     

Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety

A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety,i.e.,diamides 11,simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluo ro-containing phe nylpyrazole acid intermediate.The new compounds were identified and confirmed by melting point,1H NMR,13C NMR and elemental analysis or HRMS.The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm,diamondback moth and corn borer at low concentrations.For examples,compounds 11a,11e-g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13-0.39 mg/L and 0.0002-0.0014 mg/L against oriental armyworm and diamondback moth,respectively,were comparable with those of the control chlorantraniliprole.Particularly,lie were found superior to chlorantraniliprole in oriental armyworm tests(LC50:0.23 mg/L vs.0.26 mg/L);11a,lie,11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L,0.0002 mg/L,0.0008 mg/L and 0.0005 mg/L,respectively,we re more effective than that of chlorantraniliprole.In addition,12 a also showed a promising insecticidal potential and development/optimization advantage.Compounds 11a,lle-g,12a,14b and 14c could be considered as possible new leading structures for further study.The SAR investigation indicated that the compounds with fluorine motif(e.g.,-F,-CF2H,-CF3)held apparently favorable insecticidal potentials,which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.     

含酰基哌嗪片段的呋喃查尔酮衍生物的合成及其抗炎活性研究

依据活性结构单元的拼合原理,以2-呋喃甲醛和4-氟苯乙酮为原料出发,经Aldol缩合、脱水、哌嗪取代反应生成4’-(1-哌嗪基)呋喃查尔酮(2)后,再与酰氯和磺酰氯反应,得到了10个未见报道的含哌嗪取代的呋喃查尔酮衍生物,其结构经~1H NMR和~(13)C NMR确证。采用小鼠巨噬细胞Raw 264.7模型初步测试了目标化合物的体外抗炎活性,结果表明,磺酰胺类化合物的抗炎活性要优于酰胺类化合物,特别是化合物4d能有效抑制NO的生成(IC_(50)=3.88μmol/L),与阳性对照药地塞米松活性相当。     

Design,synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines(PC-3, LNCa P, and DU145) were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17 and 20 exhibited strong cytotoxic activities against the tested cancer cell lines(IC_(50)3 μmol/L). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure–activity relationship(SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.     

Synthesis,in-silico antiviral screening and in-vitro antibacterial screening of a novel chalcone derivatives

A new series of novel chalcones was synthesized and subjected to screening of theoretical molecular and biological properties. For evaluating the theoretical molecular properties of these molecules Molinspiration and Osiris software were used. It was concluded from data that the majority of molecules exhibited theoretical molecular and biological properties similar to that of standard drugs. Role of Hemagglutinin is vital during the attack of virus on cells so Hemagglutinin inhibitors may act as potent antiviral agents. Considering this fact in-silico studies were performed using the SwissDock screening engine on Hemagglutinin target PDB code 1HGH. Hemagglutinin inhibition potential in terms of binding affinity was expressed as ΔG values ranging from −8.71 kcal/mol to −7.39 kcal/mol. Compound IIIm showed maximum binding affinity with ΔG value −8.71 kcal/mol followed by compound IIIj ΔG value −8.31 kcal/mol. It's prudent from ΔG values that compounds may act as potent antiviral agents. Compounds were also screened for in-vitro antibacterial activity against five pathogenic strains. Most of the compounds exhibited low to moderate activity against strains under study. Compound IIIn demonstrated good activity against four pathogenic strains with highest zone of inhibition of 16 mm against K. pneumoniae and S. typhi.     

Synthesis,in vitro antibacterial and antifungal evaluation of novel 1,3,4-oxadiazole thioether derivatives bearing the 6-fluoroquinazolinylpiperidinyl moiety

A series of structurally novel 1,3,4-oxadiazole thioether derivatives(6a-6z) containing a 6-fluoroquinazolinylpiperidinyl moiety were designed and synthesized using pharmacophore hybrid approach,and their structures were fully characterized by ^1H NMR,¹³C NMR and HRMS spectra.Among them,the structure of compound 6 d was further corroborated via single-crystal X-ray diffraction analysis.In vitro antibacterial bioassays showed that compounds 6 a,6 g,6 u and 6 v possessed EC₅₀ values of 30.4,30.6,27.5 and 26.0 μg/mL against phytopathogenic bacterium Xanthomonas oryzae pv.oryzae,respectively,which were significantly superior to that of commercially-available bactericide Bismerthiazol(85.1 μg/mL).Moreover,in vitro antifungal bioassays indicated that seven compounds demonstrated broad-spectrum fungicidal acitivties against six types of phytopathogenic fungi at 50 μg/mL.The present work showed the potential of 1,3,4-oxadiazole thioether derivatives carrying a 6-fluoroquinazolinylpiperidinyl moiety as effective antimicrobial agents for crop protection,deserving further investigations in the future.     

Design,synthesis and antimycobacterial activity of novel nitrobenzamide derivatives

We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values of0.016 μg/mL against both drug-sensitive MTB strain H37 Rv and two drug-resistant clinical isolates as PBTZ169 and the lead 1, but also acceptable safety indices (SI 1500), opening a new direction for further development.     

Synthesis and antitumor activity of novel pyridazinone derivatives containing 1,3,4-thiadiazole moiety

Abstract

A series of novel pyridazinone derivatives containing the 1,3,4-thiadiazole moiety were synthesized and characterized by ¹H NMR, 13C NMR, spectroscopies HRMS and IR. Among them, the structure of compound 5c (2-(Tert-butyl)?4-chloro-5-((5-((2-ethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was unambiguously confirmed via single crystal X-ray diffraction analysis. The inhibitory activity of all the target compounds against MGC-803 and Bcap-37 was determined by MTT assay, with doxorubicin (the inhibition rates were 95.5?±?0.4% and 95.7?±?1.0% respectively) as a control. The preliminary results showed that the inhibitory activity of compound 5n (2-(Tert-butyl)?4-chloro-5-((5-((3-fluorophenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One) was superior to the others. The inhibition rates of MGC-803 and Bcap-37 cells were 86.3?±?2.2% and 92.3?±?0.6% at a concentration of 10?μmol/L, respectively. The preliminary structure-activity relationship showed that when the 2-position of the benzene ring was substituted by a methyl group, such as compound 5j (2-(Tert-butyl)?4-chloro-5-((5-((2,3-dimethylphenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5?m (2-(Tert-butyl)?4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)?1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells.