Xiaobin Wang

Bio: Xiaobin Wang is an academic researcher from Nanjing Agricultural University. The author has contributed to research in topics: Moiety & Pyrazole. The author has an hindex of 10, co-authored 29 publications receiving 231 citations. Previous affiliations of Xiaobin Wang include Guizhou University.

Synthesis and biological activity of myricetin derivatives containing 1,3,4-thiadiazole scaffold

Abstract: Myricetin and 1,3,4-thiadiazole derivatives were reported to exhibit favorable antiviral and antibacterial activities. Aiming to discover novel myricetin analogues with potent activities, a series of novel myricetin derivatives containing 1,3,4-thiadiazole moiety were synthesized, and their antibacterial and antiviral activities were evaluated. Bioassay results indicated that some target compounds exhibited potential antibacterial and antiviral activities. Among them, compounds 2, 3a, 3b, 3d, 3f, 3i, 3m and 3p exhibited excellent antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo), with EC50 values of 42.7, 38.6, 20.8, 12.9, 22.7, 27.3, 18.3 and 29.4 μg/mL, respectively, which were better than that of thiadiazole-copper (94.9 μg/mL). Compounds 3b, 3d, 3e, 3f, 3i and 3o showed good antibacterial activities against Ralstonia solanacearum (Rs), with EC50 values of 37.9, 72.6, 43.6, 59.6, 60.6 and 39.6 μg/mL, respectively, which were superior to that of thiadiazole-copper (131.7 μg/mL). In addition, compounds 3d, 3f, 3i and 3m showed better curative activities against tobacco mosaic virus (TMV), with EC50 values of 152.8, 99.7, 127.1, and 167.3 μg/mL, respectively, which were better than that of ningnanmycin (211.1 μg/mL). A series of myricetin derivatives containing 1,3,4-thiadiazole scaffold were synthesized, and their antibacterial activities against Xoo and Rs and their antiviral activity against TMV were evaluated. Bioassays indicated that some target compounds exhibited potential antibacterial and antiviral activities. These results indicated this kind of myricetin analogues could be further studied as potential alternative templates in the search for novel antibacterial and antiviral agents.

Expedient Discovery for Novel Antifungal Leads Targeting Succinate Dehydrogenase: Pyrazole-4-formylhydrazide Derivatives Bearing a Diphenyl Ether Fragment.

Abstract: The pyrazole-4-carboxamide scaffold containing a flexible amide chain has emerged as the molecular skeleton of highly efficient agricultural fungicides targeting succinate dehydrogenase (SDH). Based on the above vital structural features of succinate dehydrogenase inhibitors (SDHI), three types of novel pyrazole-4-formylhydrazine derivatives bearing a diphenyl ether moiety were rationally conceived under the guidance of a virtual docking comparison between bioactive molecules and SDH. Consistent with the virtual verification results of a molecular docking comparison, the in vitro antifungal bioassays indicated that the skeleton structure of title compounds should be optimized as an N'-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide scaffold. Strikingly, N'-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide derivatives 11o against Rhizoctonia solani, 11m against Fusarium graminearum, and 11g against Botrytis cinerea exhibited excellent antifungal effects, with corresponding EC50 values of 0.14, 0.27, and 0.52 μg/mL, which were obviously better than carbendazim against R. solani (0.34 μg/mL) and F. graminearum (0.57 μg/mL) as well as penthiopyrad against B. cinerea (0.83 μg/mL). The relative studies on an in vivo bioassay against R. solani, bioactive evaluation against SDH, and molecular docking were further explored to ascertain the practical value of compound 11o as a potential fungicide targeting SDH. The present work provided a non-negligible complement for the structural optimization of antifungal leads targeting SDH.

Novel Pyrazole-4-acetohydrazide Derivatives Potentially Targeting Fungal Succinate Dehydrogenase: Design, Synthesis, Three-Dimensional Quantitative Structure-Activity Relationship, and Molecular Docking.

Abstract: Succinate dehydrogenase inhibitors (SDHIs) have emerged in fungicide markets as one of the fastest-growing categories that are widely applied in agricultural production for crop protection. Currently, the structural modification focusing on the flexible amide link of SDHI molecules is being gradually identified as one of the innovative strategies for developing novel highly efficient and broad-spectrum fungicides. Based on the above structural features, a series of pyrazole-4-acetohydrazide derivatives potentially targeting fungal SDH were constructed and evaluated for their antifungal effects against Rhizoctonia solani, Fusarium graminearum, and Botrytis cinerea. Strikingly, the in vitro EC50 values of constructed pyrazole-4-acetohydrazides 6w against R. solani, 6c against F. graminearum, and 6f against B. cinerea were, respectively, determined as 0.27, 1.94, and 1.93 μg/mL, which were obviously superior to that of boscalid against R. solani (0.94 μg/mL), fluopyram against F. graminearum (9.37 μg/mL), and B. cinerea (1.94 μg/mL). Concurrently, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields on structure-activity relationships were elaborated by the reliable comparative molecular field analysis and comparative molecular similarity index analysis models. Subsequently, the practical value of pyrazole-4-acetohydrazide derivative 6w as a potential SDHI was ascertained by the relative surveys on the in vivo anti-R. solani preventative efficacy, inhibitory effects against fungal SDH, and molecular docking studies. The present results provide an indispensable complement for the structural optimization of antifungal leads potentially targeting SDH.

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

Abstract: 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) A, b = 10.136 (7) A, c = 10.396 (7) A, α = 118.323 (7)°, β = 91.750 (8)°, γ = 104.198 (7)°, Z = 2, V = 800.2 (9) A3; 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.

Design, Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of Novel Indolinedione-Coumarin Molecular Hybrids.

Abstract: Keeping in view various pharmacological attributes of indole and coumarin derivatives, a new series of indolindione–coumarin molecular hybrids was rationally designed and synthesized. All synthesiz...

Radiosensitizing effect of curcumin-loaded lipid nanoparticles in breast cancer cells

Abstract: In breast cancer (BC) care, radiotherapy is considered an efficient treatment, prescribed both for controlling localized tumors or as a therapeutic option in case of inoperable, incompletely resected or recurrent tumors. However, approximately 90% of BC-related deaths are due to the metastatic tumor progression. Then, it is strongly desirable to improve tumor radiosensitivity using molecules with synergistic action. The main aim of this study is to develop curcumin-loaded solid nanoparticles (Cur-SLN) in order to increase curcumin bioavailability and to evaluate their radiosensitizing ability in comparison to free curcumin (free-Cur), by using an in vitro approach on BC cell lines. In addition, transcriptomic and metabolomic profiles, induced by Cur-SLN treatments, highlighted networks involved in this radiosensitization ability. The non tumorigenic MCF10A and the tumorigenic MCF7 and MDA-MB-231 BC cell lines were used. Curcumin-loaded solid nanoparticles were prepared using ethanolic precipitation and the loading capacity was evaluated by UV spectrophotometer analysis. Cell survival after treatments was evaluated by clonogenic assay. Dose–response curves were generated testing three concentrations of free-Cur and Cur-SLN in combination with increasing doses of IR (2–9 Gy). IC50 value and Dose Modifying Factor (DMF) was measured to quantify the sensitivity to curcumin and to combined treatments. A multi-“omic” approach was used to explain the Cur-SLN radiosensitizer effect by microarray and metobolomic analysis. We have shown the efficacy of the Cur-SLN formulation as radiosensitizer on three BC cell lines. The DMFs values, calculated at the isoeffect of SF = 50%, showed that the Luminal A MCF7 resulted sensitive to the combined treatments using increasing concentration of vehicled curcumin Cur-SLN (DMF: 1,78 with 10 µM Cur-SLN.) Instead, triple negative MDA-MB-231 cells were more sensitive to free-Cur, although these cells also receive a radiosensitization effect by combination with Cur-SLN (DMF: 1.38 with 10 µM Cur-SLN). The Cur-SLN radiosensitizing function, evaluated by transcriptomic and metabolomic approach, revealed anti-oxidant and anti-tumor effects. Curcumin loaded- SLN can be suggested in future preclinical and clinical studies to test its concomitant use during radiotherapy treatments with the double implications of being a radiosensitizing molecule against cancer cells, with a protective role against IR side effects.