Therapeutic Applications of Functional Nanomaterials for Prostatitis.

Prostatitis is a common disease in adult males, with characteristics of a poor treatment response and easy recurrence, which seriously affects the patient's quality of life. The prostate is located deep in the pelvic cavity, and thus a traditional infusion or other treatment methods are unable to easily act directly on the prostate, leading to poor therapeutic effects. Therefore, the development of new diagnostic and treatment strategies has become a research hotspot in the field of prostatitis treatment. In recent years, nanomaterials have been widely used in the diagnosis and treatment of various infectious diseases. Nanotechnology is a promising tool for 1) the accurate diagnosis of diseases; 2) improving the targeting of drug delivery systems; 3) intelligent, controlled drug release; and 4) multimode collaborative treatment, which is expected to be applied in the diagnosis and treatment of prostatitis. Nanotechnology is attracting attention in the diagnosis, prevention and treatment of prostatitis. However, as a new research area, systematic reviews on the application of nanomaterials in the diagnosis and treatment of prostatitis are still lacking. In this mini-review, we will highlight the treatment approaches for and challenges associated with prostatitis and describe the advantages of functional nanoparticles in improving treatment effectiveness and overcoming side effects.

Synthesis, bioactivity and mode of action of 5A 5B 6C tricyclic spirolactones as novel antiviral lead compounds.

BACKGROUND: Plant viral diseases cause tremendous decreases in yield and quality. Natural polycyclic compounds such as those containing carbocycles are often very important lead compounds for drug and pesticide development. Tricyclic spiranoid lactones with 5A 5B 6C -ring fusion topologies possess various bioactivities. In this study, 33 new 5A 5B 6C tricyclic spirolactones were rationally designed, synthesized, characterized and evaluated for antiviral activities. RESULT: These compounds showed no apparent toxicity against Italian honeybees up to 2.73 µg bee-1 . Spirolactones 14, 16, 19, 23 and 28 at a concentration of 100 µg mL-1 inactivated 90% of tobacco mosaic virus (TMV) infection, making these compounds much more potent than the positive controls. Significantly, compound 19 displayed the best inactivation activity causing inhibition of up to 98%. CONCLUSION: The results of the bioassays and QSAR studies indicated that the carbon-containing cyclic moiety was the antiviral pharmacophore, and derivative 19, which showed the best inactivation activity, could emerge as a potential antiviral agent against TMV. In vitro capsid protein (CP) assembly and TMV assembly inhibition determinations indicated that these compounds induced crosslinking in the TMV and prevented its uncoating, which was a putative new mode of action for TMV inactivation. © 2018 Society of Chemical Industry.

Design, synthesis and fungicidal activity of isothiazole-thiazole derivatives.

3,4-Dichloroisothiazoles can induce systemic acquired resistance (SAR) to enhance plant resistance against a subsequent pathogen attack, and oxathiapiprolin exhibits excellent anti-fungal activity against oomycetes targeting at the oxysterol-binding protein. To discover novel chemicals with systemic acquired resistance and fungicidal activity, 21 novel isothiazole-thiazole derivatives were designed, synthesized and characterized according to the active compound derivatization method. Compound 6u, with EC50 values of 0.046 mg L-1 and 0.20 mg L-1 against Pseudoperonospora cubensis (Berk. et Curt.) Rostov and Phytophthora infestans in vivo, might act at the same target as oxysterol binding protein (PcORP1) of oxathiapiprolin; this result was validated by cross-resistance and molecular docking studies. The expression of the systemic acquired resistance gene pr1 was significantly up-regulated after treating with compound 6u for 24 h (43-fold) and 48 h (122-fold). These results can help the development of isothiazole-thiazole-based novel fungicides.

Synthesis of 1,2,3-Thiadiazole and Thiazole-Based Strobilurins as Potent Fungicide Candidates.

Strobilurin fungicides play a crucial role in protecting plants against different pathogens and securing food supplies. A series of 1,2,3-thiadiazole and thiazole-based strobilurins were rationally designed, synthesized, characterized, and tested against various fungi. Introduction of 1,2,3-thiadiazole greatly improved the fungicidal activity of the target molecules. Compounds 8a, 8c, 8d, and 10i exhibited a relatively broad spectrum of fungicidal activity. Compound 8a showed excellent activities against Gibberella zeae, Sclerotinia sclerotiorum, and Rhizoctonia cerealis with median effective concentrations (EC50) of 2.68, 0.44, and 0.01 µg/mL, respectively; it was much more active than positive controls enestroburin, kresoxim-methyl, and azoxystrobin with EC50 between 0.06 and 15.12 µg/mL. Comparable or better fungicidal efficacy of compound 8a compared with azoxystrobin and trifloxystrobin against Sphaerotheca fuliginea and Pseudoperonspera cubensis was validated in cucumber fields at the same application dosages. Therefore, compound 8a is a promising fungicidal candidate worthy of further development.

Synthesis and biological activity of organotin 4-methyl-1,2,3-thiadiazole-5-carboxylates and benzo[1,2,3]thiadiazole-7-carboxylates.

A series of organotin 4-methyl-1,2,3-thiadiazole-5-carboxylates and benzo[1,2,3]thiadiazole-7-carboxylates have been synthesized and characterized by NMR ((1)H, (13)C, and (119)Sn), IR, and elemental analyses. The structure of the dimeric complex {[(BTHCO(2))SnEt(2)](2)O}(2) (BTH represents benzo[1,2,3]thiadiazol-7-yl) has been further confirmed by X-ray diffraction crystallography. Assessment for fungicidal activity indicates that all of the newly synthesized compounds exhibit good growth inhibition against Alternaria solani , Cercospora arachidicola , Gibberella zeae , Physalospora piricola , and Botrytis cinerea . High growth inhibition percentage at 50 microg/mL was obtained in vitro in the case of triorganotin 4-methyl-1,2,3-thiadiazole-5-carboxylates and benzo[1,2,3]thiadiazole-7-carboxylates. The corresponding EC(50) values of these triorganotin carboxylates have been detected, and values of EC(50) as low as 0.12 microg/mL against P. piricola and 0.16 microg/mL against G. zeae, respectively, were observed for triethyltin benzo[1,2,3]thiadiazole-7-carboxylate.

Herbicide activity of monosulfuron and its mode of action.

Monosulfuron was developed for weed control in the field of wheat (Triticum, aestivum L.) and millet (Panicum miliaceum L.) with the application rate ranging from 15 to 60 g ai/hm2. Herbicidal activity of monosulfuron was evaluated systematically by bioassay using maize (Zea mays L.) taproot as indicator and weed fresh weight of Acalypha australis L. and Echinochloa phyllopogon. Maize CAU 3138 was the most tolerant cultivars to monosulfuron with IC50 (concentration of 50% inhibition) of 85 microg/kg, Yedan 13 was one of the most sensitive cultivars to monosulfuron with IC50 of 6.4 microg/kg. Monosulfuron inhibited the growth of Acalypha australis L. strongly comparing with that of Echinochloa phyllopogon. Monosulfuron was a good acetolactate synthase (ALS) inhibitor in vitro, the I50 (50% of inhibition) of monosulfuron, chlorsulfuron, tribenuron-methyl and nicosulfuron for CAU 3138 were 32, 2, 19 and 26 nmol/L respectively, for Yedan 13 the I50 were 15, 3, 17 and 65 nmol/L respectively. In vivo ALS inhibition occurred only in higher concentration of 4 sulfonylurea herbicide tested. Comparison study of this test indicated that the mode of action of monosulfuron was the same as that of other sulfonylurea herbicides such as chlorsulfuron, tribenuron-methyl and nicosulfuron, they were all inhibitors targeted at the ALS.

Synthesis and fungicidal activity of novel 2-oxocycloalkylsulfonylureas.

A series of 2-oxocycloalkylsulfonylureas (2) have been synthesized in a six-step, three-pot reaction sequence from readily available cyclododecanone, cycloheptanone, and cyclohexanone. Their structures were confirmed by IR, 1H NMR, and elemental analysis. The bioassay indicated that some of them possess certain fungicidal activity against Gibberella zeae Petch. In general, compounds containing a 12-membered ring (2A) are more active than those containing a 6- or 7-membered ring (2B, 2C). In the series 2A, the compounds in which R is a disubstituted phenyl or pyrimidyl showed better activity than those in which R is a monosubstituted phenyl or pyrimidyl, and aryl-substituted compounds have somewhat higher activity than those substituted by pyrimidyl. The further bioassay showed that the representative of 2A, 2A15, has good fungicidal activities against not only G. zeae Petch but also Botrytis cinerea Pers, Colletotrichum orbiculare Arx, Pythium aphanidermatum Fitzp, Fusarium oxysporum Schl. f. sp. Vasinfectum, etc.

Residue analysis and dissipation of monosulfuron in soil and wheat.

HPL-UV residue analytical method for monosulfuron [N-[(4'-methyl) pyrimidin-2'yl]-2-nitrophenylsulfonyl urea] in soil and wheat was developed. Monosulfuron residues were recovered by solvent extraction, followed by liquid-liquid partition, and C18 cartrige clean-up. Excellent method recoveries ranging from 95%-104% for both fortified soil and wheat grain were obtained with coefficients of variation 1.5%-11.8%. The minimum detectable quantities in soil and wheat were both 4 ng, the limit of detection was 0.02 mg/kg. When monosulfuron was applied according to double dosage of maximum recommended use direction(120 g ai/hm2 of 10% monosulfuron wettable powder sprayed for once during development of wheat) in field studies conducted in Shandong Province and near Beijing, monosulfuron residues was not detected in soil and wheat samples collected 75 d after application. Laboratory soil degradation studies showed that monosulfuron degraded faster in acidic soil and strong alkaline soil than in neutral or weak alkaline soil. Half lives in Jiangxi soil, Shijiazhuang soil, Jiangsu soil and Heilongjiang soil were 41, 48, 87 and 84 d respectively. Monosulfuron residues dissipated rapidly in Shandong and Beijing field test sites with half-lives of less than 14 d.