Study on the Design, Synthesis, Bioactivity and Translocation of the Conjugates of Phenazine-1-carboxylic Acid and N-Phenyl Alanine Ester.

The natural pesticide phenazine-1-carboxylic acid (PCA) is known to lack phloem mobility, whereas Metalaxyl is a representative phloem systemic fungicide. In order to endow PCA with phloem mobility and also enhance its antifungal activity, thirty-two phenazine-1-carboxylic acid-N-phenylalanine esters conjugates were designed and synthesized by conjugating PCA with the active structure N-acylalanine methyl ester of Metalaxyl. All target compounds were characterized by 1H NMR, 13C NMR and HRMS. The antifungal evaluation results revealed that several target compounds exhibited moderate to potent antifungal activities against Sclerotinia sclerotiorum, Bipolaris sorokiniana, Phytophthora parasitica, Phytophthora citrophthora. In particular, compound F7 displayed excellent antifungal activity against S. sclerotiorum with an EC50 value of 6.57 µg/mL, which was superior to that of Metalaxyl. Phloem mobility study in castor bean system indicated good phloem mobility for the target compounds F1-F16. Particularly, compound F2 exhibited excellent phloem mobility; the content of compound F2 in the phloem sap of castor bean was 19.12 µmol/L, which was six times higher than Metalaxyl (3.56 µmol/L). The phloem mobility tests under different pH culture solutions verified the phloem translocation of compounds related to the "ion trap" effect. The distribution of the compound F2 in tobacco plants further suggested its ambimobility in the phloem, exhibiting directional accumulation towards the apical growth point and the root. These results provide valuable insights for developing phloem mobility fungicides mediated by exogenous compounds.

Design, Synthesis, Antibacterial, and Antifungal Evaluation of Phenylthiazole Derivatives Containing a 1,3,4-Thiadiazole Thione Moiety.

To effectively control the infection of plant pathogens, we designed and synthesized a series of phenylthiazole derivatives containing a 1,3,4-thiadiazole thione moiety and screened for their antibacterial potencies against Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, as well as their antifungal potencies against Sclerotinia sclerotiorum, Rhizoctonia solani, Magnaporthe oryzae and Colletotrichum gloeosporioides. The chemical structures of the target compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioassay results revealed that all the tested compounds exhibited moderate-to-excellent antibacterial and antifungal activities against six plant pathogens. Especially, compound 5k possessed the most remarkable antibacterial activity against R. solanacearum (EC50 = 2.23 µg/mL), which was significantly superior to that of compound E1 (EC50 = 69.87 µg/mL) and the commercial agent Thiodiazole copper (EC50 = 52.01 µg/mL). Meanwhile, compound 5b displayed the most excellent antifungal activity against S. sclerotiorum (EC50 = 0.51 µg/mL), which was equivalent to that of the commercial fungicide Carbendazim (EC50 = 0.57 µg/mL). The preliminary structure-activity relationship (SAR) results suggested that introducing an electron-withdrawing group at the meta-position and ortho-position of the benzene ring could endow the final structure with remarkable antibacterial and antifungal activity, respectively. The current results indicated that these compounds were capable of serving as promising lead compounds.

Design, synthesis and antifungal evaluation of phenylthiazole-1,3,4-oxadiazole thione (ketone) derivatives inspired by natural thiasporine A.

BACKGROUND: Plant pathogenic fungal infections have become a severe threat to the yield and quality of agricultural products, and new green antifungal agents with high efficiency and low toxicity are needed. In this study, a series of thiasporine A derivatives containing phenylthiazole-1,3,4-oxadiazole thione (ketone) structures were designed and synthesized, and their antifungal activities against six invasive and highly destructive phytopathogenic fungi were evaluated. RESULTS: The results found that all compounds showed moderate to potent antifungal activity against six phytopathogenic fungi, and most of the E series compounds showed remarkable antifungal activity against Sclerotinia sclerotiorum and Colletotrichum camelliaet. In particular, compounds E1-E5, E7, E8, E13, E14, E17, and E22 showed more significant antifungal activity against S. sclerotiorum, with half-maximal effective concentration (EC50 ) values of 0.22, 0.48, 0.56, 0.65, 0.51, 0.39, 0.60, 0.56, 0.60, 0.63, and 0.45 µg mL-1 , respectively, which were superior to that of carbendazim (0.70 µg mL-1 ). Further activity studies showed that compound E1 possessed superior curative activities against S. sclerotiorum in vivo and better inhibitory effects on sclerotia germination and the formation of S. sclerotiorum compared with those of carbendazim. CONCLUSIONS: This study indicates that these thiasporine A derivatives containing phenylthiazole-1,3,4-oxadiazole thione structures might be used as antifungal agents against S. sclerotiorum. © 2023 Society of Chemical Industry.

α-melanocyte stimulating hormone (α-MSH) promotes osteoblast differentiation of MC3T3-E1 cells.

α-melanocyte stimulating hormone (α-MSH) is a member of the melanocortin family, that has displayed important biological functions in diverse cells and tissues. The purpose of this study is to test the effect of α-MSH on the differentiation and mineralization of osteoblast cells. The expression of the α-MSH membrane receptor MC1R but not MC2R, MC3R, or MC4R increased distinctively during the osteogenic differentiation from 3, 7 to 14 d. Treatment with α-MSH promoted the differentiation and mineralization of MC3T3-E1 cells by increasing the activity of ALP, enhancing Alizarin Red S staining, and stimulating the expression of osteogenic genes, including ALP1, osteocalcin (Bglap2), and osterix (Sp7). Importantly, we found that α-MSH increased the expression of Runx-2, a master transcriptional factor of osteogenic differentiation. Mechanically, we found that the activation of ERK1/2 was involved in this process. Using the small interfering (si) RNA knockdown experiment, we proved that the effects of α-MSH on differentiation and mineralization of osteoblast cells are mediated by MC1R. The present study proposes α-MSH as a potential therapeutic agent to stimulate bone formation for osteoporosis and bone defect. Meanwhile, MC1R could also be a target candidate for the treatment of bone metabolism diseases.

[Artificial femoral head replacement for the treatment of unstable intertrochanteric fractures in aged patients: a report 40 cases].

OBJECTIVE: To study the operative procedures, indicatrions and short-term effects of the artificial femoral head replacement for the treatment of unstable intertrochanteric fracture in aged patients. METHODS: From January 2001 to October 2008, 40 patients with unstable intertrochanteric fractures were treated with artificial femoral head replacement. Among the patients, 9 patients were male and 31 patients were female, ranging in age from 75 to 95 years, averaged 81.1 years. The duration from injured to the hospitalization ranged from 3 to 48 hours, with a mean of 11.5 h. According to Evans classification, 8 patients were type II , 21 type III, and 11 type IV. The duration from hospitalization to operation ranged from 4 to 8 days, averaged 4.8 day. After the operation, the hip motion was observed and the preoperative and postoperative Harris scores were compared. RESULTS: All the patients were operated successfully, and were kept in bed about 4 to 7 days, 5.9 days in average. Thirty-one patients were followed up for 6 months without loose or dislocation of prothesis, periprosthetic fractures. Fourteen patients resumed to normal activity of the hip joint while 17 patients showed the declination of hip movement. Their hip movements recovered to (66.67+/-26.35)% at 4 months after operations and (76.08+/-25.62)% at 6 months. Among 10 patients with normal ability of hip joints before their injuries were valuated with Harris system at 6 mouths after operations, the results were:5 excellent, 3 good and 2 poor. CONCLUSION: Artificial femoral head replacement for unstable intertrochanteric fractures in aged patients is effective in the recovery of hip joint function in short time with earlier walking and decreased complications.