Piperazine-Coumarin based fluorescence probe with enhanced brightness and solubility for bio-thiol detection and esophageal carcinoma diagnosis.

The development of novel fluorescent dyes for bio-thiol is of great importance in biological, clinical and pharmaceutical sciences. Given the importance of bio-thiol anticipating in numerous physiological processes, there is a great need to construct fluorescent biosensors with high quality to detect them. Fluorophores, especially those used in bio-system, usually require high-quality properties such as high brightness, good water solubility, bio-compatible and photostability. Herein, we reported a novel fluorescent probe based on piperazine-coumarin scaffold with enhanced brightness and solubility. To further demonstrate the potential clinical applications, we performed living cell fluorescence image and human esophageal carcinoma diagnosis. The result indicated that we were able to distinguish pathological tissue from normal tissue by applying this probe. Thus, we hope this design will be helpful to develop high-quality fluorophores for clinical diagnosis.

Novel carboxylated pyrroline-2-one derivatives bearing a phenylhydrazine moiety: Design, synthesis, antifungal evaluation and 3D-QSAR analysis.

Aiming to discover novel high-efficient antifungal leads that possess an innovative action mechanism, twenty-three carboxylated pyrroline-2-one derivatives, bearing a phenylhydrazine moiety, were rationally designed and firstly prepared in this letter. The in vitro bioassays showed that most of the compounds possessed excellent antifungal effects with the EC50 values of less than 1 µg/mL against the phytopathogenic fungi Fusarium graminearum (Fg), Botrytis cinerea (Bc), Rhizoctonia solani (Rs) and Colletotrichum capsici (Cc). The further bioassays showed that the compound 6u showed the comparable in vivo control effect with carbendazim against fusarium head blight and rice sheath blight. The 3D-QSAR model revealed the pivotal effects of a bulky electron-donating group at the 1-position of pyrrole ring, a bulky electron-withdrawing group at the 4-position of phenyl ring and a small alkyl at the carbonate group on the anti-Rs activities of target compounds. The abnormal mycelial morphology and delayed spore germination were observed in the treatments of compound 6u. Given the excellent and broad-spectrum antifungal effects the target compounds have, we unfeignedly anticipated that the above finding could motivate the discovery of high-efficient antifungal leads, which might possess an innovative action mechanism against phytopathogenic fungi.

Design, synthesis and antimicrobial activities of novel 1,3,5-thiadiazine-2-thione derivatives containing a 1,3,4-thiadiazole group.

A series of novel 1,3,5-thiadiazine-2-thione derivatives containing a 1,3,4-thiadiazole group was designed and synthesized. The structures of all the compounds were well characterized using 1H NMR, 13C NMR and high-resolution mass spectrometer, and further confirmed by the X-ray diffraction analysis of 8d. The antimicrobial activities of all the target compounds against Xanthomonas oryzae pv. oryzicola, X. oryzae pv. oryzae, Rhizoctonia solani and Fusarium graminearum were evaluated. The in vitro antimicrobial bioassays indicated that some title compounds exhibited noteworthy antimicrobial effects against the above strains. Notably, the compound N-(5-(ethylthio)-1,3,4-thiadiazol-2-yl)-2-(5-methyl-6-thioxo-1,3,5-thiadiazinan-3-yl)acetamide (8a) displayed obvious antibacterial effects against X. oryzae pv. oryzicola and X. oryzae pv. oryzae at 100 µg/mL with the inhibition rates of 30% and 56%, respectively, which was better than the commercial bactericide thiodiazole-copper. In addition, the anti-R. solani EC50 value of 8a was 33.70 µg/mL, which was more effective than that of the commercial fungicide hymexazol (67.10 µg/mL). It was found that the substitutes in the 1,3,5-thiadiazine-2-thione and the 1,3,4-thiadiazole rings played a vital role in the antimicrobial activities of the title compounds. More active title compounds against phytopathogenic microorganisms might be obtained via further structural modification.

Design and synthesis of novel 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives bearing a hydrazone moiety as potential fungicides.

BACKGROUND: Tetramic acid, thiophene and hydrazone derivatives were found to exhibit favorable antifungal activity. Aiming to discover novel template molecules with potent antifungal activity, a series of novel 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives containing a hydrazone group were designed, synthesized, and evaluated for their antifungal activity. RESULTS: The structures of 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives bearing a hydrazone group were confirmed by FT-IR, 1H NMR, 13C NMR, 1H-1H NOESY, EI-MS and elemental analysis. Antifungal assays indicated that some title compounds exhibited antifungal activity against Fusarium graminearum (Fg), Rhizoctorzia solani (Rs), Botrytis cinerea (Bc) and Colletotrichum capsici (Cc) in vitro. Strikingly, the EC50 value of 5e against Rs was 1.26 µg/mL, which is better than that of drazoxolon (1.77 µg/mL). Meanwhile, title compounds 5b, 5d, 5e-5g, 5n-5q and 5t exhibited remarkable anti-Cc activity, with corresponding EC50 values of 7.65, 9.97, 6.04, 6.66, 7.84, 7.59, 9.47, 5.52, 6.41 and 7.53 µg/mL, respectively, which are better than that of drazoxolon (19.46 µg/mL). CONCLUSIONS: A series of 3-(thiophen-2-yl)-1,5-dihydro-2H-pyrrol-2-one derivatives bearing a hydrazone group were designed, synthesized and evaluated for their antifungal activity against Fg, Rs, Bc and Cc. Bioassays indicated that some target compounds exhibited obvious antifungal activity against the above tested fungi. These results provide a significant basis for the further structural optimization of tetramic acid derivatives as potential fungicides.

Synthesis, Characterization, and Antifungal Activity of Novel Benzo[4,5]imidazo[1,2-d][1,2,4]triazine Derivatives.

A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4]triazine 4a-4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a-3g. The structures of all target compounds were characterized by FT-IR, ¹H NMR, 13C NMR, and EI-MS, of which, the structure of compound 4n was further determined by the single crystal X-ray diffraction. The crystal structure of 4n was crystallized in the triclinic crystal system, space group P 1 ¯ with a = 9.033 (6) Å, b = 10.136 (7) Å, c = 10.396 (7) Å, α = 118.323 (7)°, ß = 91.750 (8)°, γ = 104.198 (7)°, Z = 2, V = 800.2 (9) ų; total R indices: R1 = 0.0475, wR2 = 0.1284. The antifungal activity of title compounds 4a-4w in vitro against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the bioassay results demonstrated that most of the title compounds exhibited obvious fungicidal activities at 50 µg/mL. This work indicated that benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new leading structure in searching for novel agricultural fungicides.

Synthesis and fungicidal activity of phenylhydrazone derivatives containing two carbonic acid ester groups.

Substituted phenylhydrazone moieties and two carbonate groups were merged in one molecule scaffold to obtain 48 novel compounds. 1H and 13C NMR, MS, elemental analysis, and X-ray single-crystal diffraction were used to confirm their structures. Bioassay results revealed that some of the compounds have strong antifungal activities against Botrytis cinerea, Rhizoctonia solani, and Colletotrichum capsici (especially Rhizoctonia solani). Compound 5H1 is the most promising of the tested compounds against R. solani with an EC50 value of 1.91 mg/L, which is comparable with the positive control fungicide drazoxolon (1.94 mg/L). The structure-activity relationships against R. solani formed three rules: 1) small carbonate groups may improve the antifungal activity of the title compounds; 2) electron-withdrawing groups at the phenyl ring of phenylhydrazone are preferable to their non-substituted counterparts; and 3) halogen at the para position is more beneficial than at the ortho or meta position.

Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors.

A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44 nM and 13.58 nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study.

Synthesis and biological activity of novel benzimidazole derivatives as potential antifungal agents.

In the present study, a series of novel benzimidazole derivatives containing chrysanthemum acid moieties was designed and synthesized. Preliminary investigation of biological activity indicated that all of the compounds exhibited lower activity than that of beta-cypermethrin against Plutella xylostella and Lipaphis erysimi; meanwhile, they showed good inhibitory activity against Botrytis cinerea and Sclerotinia sclerotiorum in vitro. The fungicidal activity of compound 8a against B. cinerea was approximately equal to that of thiabendazole and was twice as active against S. sclerotiorum as was thiabendazole. In addition, compound 9e displayed the most potent inhibitory activity against both fungi and was almost twice as potent as thiabendazole.