Lepidopteran species cause significant harm to agricultural yields and food quality. In this study, a series of innovative isoxazoline derivatives incorporating pyrazolamide moieties were carefully designed and synthesized as potential insecticidal agents. Among these, compound F16 demonstrated an LC₅₀ value of 0.01 mg/L against Plutella xylostella, surpassing that of the lead compound fluxametamide (LC₅₀ = 0.15 mg/L). Furthermore, F16 exhibited broad-spectrum insecticidal activity against Pyrausta nubilalis, Spodoptera frugiperda, Chilo suppressalis, Aphis craccivora, and Sogatella furcifera. Notably, F16 possessed low toxicity against Danio rerio, whereas fluxametamide displayed moderate toxicity. Furthermore, molecular docking analysis demonstrated that the potent insecticidal activity of F16 is likely mediated by its specific interactions with γ-GABA receptors primarily through the formation of hydrogen bonds with key residues. Density functional theory calculations and molecular electrostatic potentials were also performed to gain insights into the insecticidal behavior of F16. These findings suggest that F16 is a promising candidate for further investigation as a novel pesticide.

2024-01-25·Journal of medicinal chemistry1区 · 医学

Selective Antitumor Effect and Lower Toxicity of Mitochondrion-Targeting Derivatization of Triptolide

1区 · 医学

Article

作者: Liu, Guoliang ; Lou, Hongxiang ; Xing, Wenlan ; Fan, Peihong ; Zhang, Yue ; Zhang, Tao

Triptolide has a significant antitumor activity, but its toxicity limits its clinical application. As the mitochondrion-targeting strategy showed an advantage in selective antitumor effect based on the higher mitochondrial membrane potential (MMP) in tumor cells than normal cells, the lipophilic cations triphenylphosphonium and E-4-(1H-indol-3-yl vinyl)-N-methylpyridinium iodide (F16) were selected as targeting carriers for structural modification of triptolide. The derivatives bearing F16 generally retained most antitumor activities, overcame its inhibition plateau phenomena, and enhanced its selective antitumor effect in lung cancer. The representative derivative F9 could accumulate in the mitochondria of NCI-H1975 cells, inducing apoptosis and a dose-dependent increase in intracellular reactive oxygen species and reducing MMP. Moreover, no effects were observed in normal cells BEAS-2B. In vivo studies showed that the developmental, renal, and liver toxicities of F9 to zebrafish were significantly lower than those of triptolide. This study provides a promising idea to relieve the toxicity problem of triptolide.

2022-06-09·Journal of medicinal chemistry1区 · 医学

Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity

1区 · 医学

Article

作者: Guo, Jian ; He, Yun ; Wang, Daoqiang ; Xiang, Sichuan ; Yang, Xiaohong ; Qiu, Yanfei ; Zhang, Shao-Lin ; Huang, Chao ; Dai, Yuanwei ; Wang, Zhi-Peng ; Luo, Dong ; Zhao, Yi

Calothrixin A (CAA) is a dual Topo I and II inhibitor but exhibits poor antiproliferative activities and water solubility. Herein, a library of novel CAA analogues was synthesized. Among them, compound F16 exhibited superior water solubility (>5 mg/mL) as compared to CAA (<5 μg/mL). The mechanism of action studies confirmed that F16 acted as a dual Topo I and II poison. Furthermore, F16 displayed potent antiproliferative activities against high Topo I and II expression cell lines A375 and HCT116, with IC₅₀ values of 20 and 50 nM, respectively. In xenograft models, F16 reduced the tumor growth at a dose of 10 or 20 mg/kg without apparent effect on the mouse weight, while the clinically used Topo II inhibitor VP-16 dramatically reduced the mouse weight. Collectively, our data demonstrated that F16 could be a promising lead for the development of novel dual Topo I and II antitumor agents.

项与 Prostiazol 相关的新闻（医药）

2021-02-25

·GlobeNewswire

Top Aces Corp. Demonstrates Advanced Adversary Training Capabilities to USAFE

MESA, Ariz., Feb. 25, 2021 (GLOBE NEWSWIRE) -- On February 24th, 2021, Top Aces Corp. (Top Aces), together with Huntington Ingalls Industries, was contracted by the United States Air Force in Europe (USAFE) for fast jet adversary support at the Ramstein Air Base in Germany. Top Aces provided a 4-ship of A-4N Skyhawks to fly in USAFE’s Joint All Domain Command and Control Exercise (JADC2) in conjunction with its Advanced Battle Management System (ABMS). Operating out of the Wittmundhafen Air Base, Top Aces has served the German Armed Forces with advanced adversary training for the past 6 years. “Top Aces has built a reputation for safety, credibility and operational excellence in Germany, and we are very proud to extend our services to other NATO countries in support of USAFE training,” said Rolf Brandt, Senior Program Manager – German Operations at Top Aces. All 8 mission runs were successfully completed “on time, on target” during the exercise lead by Reic “Junior” Ferner, a Top Aces Pilot with more than 5,000 hours of combined fighter experience in the Luftwaffe and with Top Aces. Top Aces has effectively and affordably trained air force leaders throughout the world. Its mission-critical training enhances the operational readiness of combat forces by providing a realistic threat representative experience – all while prolonging its customers’ front-line fleet life and generating cost savings. “Top Aces is honored to support USAFE today and looks forward to the upcoming ADAIR (Adversary Air) Utility Assessment, where we will participate with our new radar-equipped A-4N AAF (Advanced Aggressor Fighter),” said Top Aces Corp. President Russ Quinn. Featuring a state-of-the-art Active Electronically Scanned Array (AESA) radar, Top Aces’ proprietary Advanced Aggressor Mission System (AAMS) allows its aircraft to simulate the capabilities of modern-day opponents in air-to-air combat. With flight testing and certification of the AAMS complete, Top Aces plans to start demonstrating this revolutionary new technology to its customers this summer. About Top Aces The purpose of Top Aces Corp. is to prepare the next generation of air combat leaders with advanced adversary training services. When Top Aces’ first F-16 fighters arrived at its facilities in Mesa, Arizona in early 2021, it made history as the first commercial company in the world to offer the supersonic F-16. Top Aces’ modern aggressor fleet, innovative technology, and very experienced pilots and staff provide highly professional and credible adversary air training. For further information, please visit . Media contact: Russ Quinn President, Top Aces Corp. media@topaces.com +1 480-792-6200 Photos accompanying this announcement are available at

100 项与 Prostiazol 相关的药物交易

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