Synthesis of Pyrroles and Condensed Pyrroles as Anti-Inflammatory Agents with Multiple Activities and Their Molecular Docking Study

We herein disclose a series of novel pyrrole derivatives as well as fused pyrrolopyridines 6a,b and 7a,b, pyrrolopyrazoles 8a, b, pyrrolo[2,3-d]pyrimidine derivatives 10a-d, 12a,b, 14a,b, 18a,b, 20a,b, 21a,b, 22a,b, 23a,b, 24a,b, 31a,b, 36a,b, 40a,b, pyrrolo[1,2,6]thiadiazine derivatives 19a,b, pyrrolotriazolopyrimidines 25a,b, 26a,b, 27a,b and 28a,b, pyrrolo[2,3-d][1,2,3]triazine derivatives 32a,b and pyrrolo[2,3-d][1,3]oxazine derivatives 39a,b as novel compounds. All compounds were evaluated for their anti-inflammatory, analgesic (compared to the reference drug Indomethacin) and antimicrobial activities (compared to the reference drug Ampicillin and Fluconazole). Compounds 4d, 5b-d, 6a,b, 9c,d, 10d, 12ab, 13b, 19a,b, 21b, 23b, 31a,b, 38b and 40a were found to be the most active anti-inflammatory drugs exhibiting potency ranging from 1 - 1.01 compared to the reference drug indomethacin. In addition to docking study of these highly active twenty compounds against the active site of cyclooxygenase-2 enzyme (COX-2), among the tested compounds, compounds 5d, 9d, 11b, 12a, 13b and 32a showed multiple activities;anti-inflammatory, analgesic and anti-bacterial activities.

New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

Aging-induced memory loss due to decreased N1-acetyl-5-methoxykynuramine,a melatonin metabolite,in the hippocampus:a potential prophylactic agent for dementia

Melatonin(N-acetyl-5-methoxytryptamine)is known as the hormone of darkness because it is synthesized at night and involved in regulating the circadian clock.The hormone is primarily synthesized by the vertebrate pineal gland,but is ubiquitous among invertebrates,unicellular organisms,plants,and even cyanobacteria(Hattori and Suzuki,2024).Melatonin is well-conserved evolutionarily and possesses several physiological functions,such as immune response,bone and glucose metabolism,and memory formation besides regulating the circadian rhythm.

Injectable body temperature responsive hydrogel for encephalitis treatment via sustained release of nano-anti-inflammatory agents

Skull defects are common in the clinical practice of neurosurgery,and they are easily complicated by encephalitis,which seriously threatens the life and health safety of patients.The treatment of encephalitis is not only to save the patient but also to benefit the society.Based on the advantages of injectable hydrogels such as minimally invasive surgery,self-adaptation to irregularly shaped defects,and easy loading and delivery of nanomedicines,an injectable hydrogel that can be crosslinked in situ at the ambient temperature of the brain for the treatment of encephalitis caused by cranial defects is developed.The hydrogel is uniformly loaded with nanodrugs formed by cationic liposomes and small molecule drugs dexmedetomidine hydrochloride(DEX-HCl),which can directly act on the meninges to achieve sustained release delivery of anti-inflammatory nanodrug preparations and achieve the goal of long-term anti-inflammation at cranial defects.This is the first time that DEX-HCl has been applied within this therapeutic system,which is innovative.Furthermore,this study is expected to alleviate the long-term suffering of patients,improve the clinical medication strategies for anti-inflammatory treatment,promote the development of new materials for cranial defect repair,and expedite the translation of research outcomes into clinical practice.

基于Agent人工智能的异构网络多重覆盖节点入侵检测系统设计

异构网络具有结构复杂、多重覆盖面积大等特征,使得网络入侵检测较为隐蔽,威胁网络运行的安全性;为此,对基于Agent人工智能的异构网络多重覆盖节点入侵检测系统进行了研究;通过检测Agent和通信Agent装设主机Agent,以Cisco Stealthwatch流量传感器作为异构网络传感器检测攻击行为,采用STM32L151RDT664位微控制器传输批量数据,由MAX3232芯片实现系统电平转化,实现硬件系统设计;软件部分设计入侵检测标准,采用传感器设备捕获网络实时数据,通过Agent技术解析异构网络协议并提取数据运行特征,综合考虑协议解析结果及与检测标准匹配度,实现异构网络多重覆盖节点入侵检测;经实验测试表明,基于Agent人工智能的异构网络多重覆盖节点入侵检测系统入侵行为的漏检率和入侵类型误检率的平均值仅为6%和5%,能够有效提高检测精度,减小检测误差。

基于多Agent深度强化学习的无人机协作规划方法

人机协作控制是多无人机任务规划的重要方式。考虑多无人机任务环境协同解释和策略控制一致性需求,提出基于多Agent深度强化学习的无人机协作规划方法。依据任务知识和行为状态,构建基于任务分配Agent的任务规划器,生成人机交互的相互依赖关系;设计一种深度学习强化方法,解决群体行为最优策略和协同控制方法,并利用混合主动行为选择机制评估学习策略。实验结果表明:作为人机交互实例,所提方法通过深度强化学习使群体全局联合动作表现较好,学习速度和稳定性均能优于确定性策略梯度方法。同时,在跟随、自主和混合主动3种模式比较下,可以较好地控制无人机飞行路径和任务,为无人机集群任务执行提供了智能决策依据。

流程型生产安全数据流的多Agent节点协同分流优化方法

为实现流程型生产安全监测系统的及时、准确决策,结合数据流采集与隐患识别过程,分析非关键数据的冗余、关键数据的缺失和数据计算时延较大的问题,提出基于多Agent的流程型生产安全数据流网络分流调度规划方法和节点流量划分识别机制。研究结果表明:相较于分簇传输方法,数据流网络分流调度方法可以实现关键隐患数据更高的传输成功率;相较于常规的复杂事件处理方法,本文提出的流量划分识别机制在2种类型数据集上实现隐患事件识别均有更低的计算时延。研究结果可为流程行业安全生产数字化管控模式和数据高质量获取提供参考。

Agent视域下的人工智能赋能作战系统

针对作战系统的智能化设计问题,提出了基于Agent的人工智能技术概念框架和应用方法。首先,阐述了Agent概念,讨论了在作战系统中研究Agent的重要意义。然后,介绍了基于Agent的人工智能研究框架,列举了Agent在作战系统中的多种应用方式。最后,分析了Agent技术发展趋势及其作战应用可能面临的风险与挑战。

基于AI agent的6G内生智能技术框架及其应用

未来6G网络将内生支持通信和AI一体化服务,赋能丰富多彩的新业务,支撑社会高效可持续发展。为此,借鉴了IT行业AI Agent的应用范式,基于电信应用场景创新地提出了6G AI Agent技术框架的三大设计理念,包括多模型融合、定制化Agent和插件式环境交互,并基于该理念构建了6G AI Agent技术框架。通过环境交互层、Agent引擎层、模型调度层、模型基座层交互协同,实现了自主环境感知、自主任务生成和自主执行任务的能力。此外,以移动网络的智能感知任务为例,探索了AI Agent的使用场景及价值,为AI新技术在电信领域发展提供了新的思路和技术支撑。

基于免疫Agent的电力电缆线路故障检测系统

为区别故障信号、非故障信号,实现对电缆线路故障的准确检测,设计了基于免疫Agent的电力电缆线路故障检测系统。利用前端检测电路为故障分析模块、测距方式切换模块提供电量传输信号,完成系统前端检测装置的连接。按照免疫Agent检测原理提取电力电缆线路故障信号的特征,联合已获取信号对象,求解检测插值指标的具体数值。结合各级硬件设备结构,完成系统设计。实验结果表明,该系统可同时检测波频为10~20 Hz、40~50 Hz、60~70 Hz的故障信号与波频为20~30 Hz、30~40 Hz、50~60 Hz的非故障信号,可以在精准辨别故障与非故障信号的同时,实现对电力电缆线路故障的准确检测。

基于多Agent的服装可持续消费行为建模与仿真

“双碳”目标下,随着服装消费引起的气候变化和环境污染等生态问题日益严重,迫切需要重新思考和重塑服装消费模式,推动服装消费向质量型、低碳化转变,从而实现服装产业的绿色转型。文章运用多Agent建模方法,构建服装可持续消费行为仿真模型,采用Netlogo平台进行仿真实验,探求服装可持续消费行为的影响机理。结果表明,消费者可持续消费认知、产品可持续性和设施供应条件均显著促进可持续消费行为;但不同强度下,产品可持续性和设施供应条件的推动作用存在差异。基于此,从可持续消费认知和供应条件两方面提出了引导中国消费者服装可持续消费行为的建议和对策。

一种基于Agent的任务自生成方法

任务自生成是基于预先设定的业务工作流完成任务执行流程制定的一个过程,任务执行流程制定主要包括任务执行步骤选取与任务执行步骤相应的解决方案选取。提出一种基于Agent的任务自生成方法来解决基于传统的业务工作流的流程制定机制,在面对有差异性需求的不同任务时,因其不能做出任务执行流程制定的自适应性改变而在处理任务时出现处理速度慢、结果不准确等问题。利用Agent的环境感知能力实现对任务需求信息和任务自生成系统环境的感知,利用Agent的自主行为决策能力结合感知的信息实现对任务执行流程制定工作的自主管理,在真实应用场景测试中,通过一系列比较实验验证了这种方法在处理速度和准确度方面具有明显优势。

基于Multi-Agent的无人机集群体系自主作战系统设计

针对无人集群自主作战体系设计中的关键问题,提出基于Multi-Agent的无人集群自主作战系统设计方法。建立无人集群各节点的Agent模型及其推演规则;对于仿真系统模块化和通用化的需求,设计系统互操作式接口和无人集群自主作战的交互关系;开展无人集群系统仿真推演验证。仿真结果表明,所提设计方案不仅能够有效开展并完成自主作战网络生成-集群演化-效能评估的全过程动态演示验证,而且能够通过重复随机试验进一步评估无人集群的协同作战效能,最后总结了集群协同作战的策略和经验。

Novel coumarin–benzimidazole derivatives as antioxidants and safer anti-inflammatory agents

Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles,novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position.The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile.Two series of coumarin–benzimidazole derivatives(4a–e and 5a–e)were synthesized and evaluated for anti-inflammatory activity and antioxidant activity.Compounds 4c,4d and 5a displayed good anti-inflammatory(45.45%,46.75%and 42.85%inhibition,respectively,versus 54.54% inhibition by indomethacin)and antioxidant(IC_(50) of 19.7,13.9 and 1.2 mmol/L,respectively,versus 23.4 mmol/L for butylatedhydroxytoluene)activities.Evaluation of ulcer index and in vivo biochemical estimations for oxidative stress revealed that compounds 4d and 5a remain safe on gastric mucosa and did not induce oxidative stress in tissues.Calculation of various molecular properties suggests the compounds to be sufficiently bioavailable.

Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents

Lappaconitine(LA),a natural compound with a novel C18-diterpenoid alkaloid skeleton,displayed extensive biological profile.Recent research on LA is focused mainly on its anti-tumor and analgesic effects,and therefore we aimed to investigate its anti-inflammatory potential.A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized.In the initial screening of LA derivatives against NO production,all the target compounds,except compound E2,exhibited excellent inhibitory ability relative to that of LA.Particularly,compound A4 exhibited the most potent inhibition with IC50 of 12.91 mmol/L.The elementary structureeactivity relationships(SARs)of NO inhibitory activity indicated that replacement of the benzene ring with an electron donating group could improve the anti-inflammatory efficacy.Furthermore,compound A4 shows an anti-inflammatory mechanism by inhibiting NO,PGE2,and TNF-a generation via the suppression of NF-kB and MAPK signaling pathways.Notably,compound A4 could exert a significant therapeutic effect on LPS-induced acute lung injury(ALI)in vivo.Based on the above research,we further investigated the preliminary pharmacokinetic property of A4 in rats.Therefore,compound A4 could be a promising candidate for the development of anti-inflammatory agents in the future.

Non-steroidal anti-inflammatory drugs-induced small intestinal injury and probiotic agents

Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs （NSAID）-induced small intestinal injury. Agents such as probiotics, able to modi~ the gut ecology, might theoretically be useful in preventing small intestinal damage induced by NSAIDs. The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.

Synthesis,characterization and pharmacological evaluation of pyrazolyl urea derivatives as potential anti-inflammatory agents

p38α mitogen activated protein kinase(MAPK) inhibitors provide a novel approach for the treatment of inflammatory disorders.A series of fifteen pyrazolyl urea derivatives(3a-o) were synthesized and evaluated for their p38α MAPK inhibition and antioxidant potential.Compounds 3a-e,3g and 3h showed low micromolar range potency(IC_(50) values ranging from 0.037 ±1.56 to 0.069± 0.07μmol/L)compared to the standard inhibitor SB 203580(IC_(50) = 0.043 + 3.62μmol/L) when evaluated for p38αMAPK inhibition by an immunosorbent-based assay.Antioxidant activity was measured by a 2,2'-diphenyl-1-picryl hydrazyl radical(DPPH) free radical scavenging method and one of the compounds,3c,showed better percentage antioxidant activity(75.06%) compared to butylated hydroxy anisole(71.53%)at 1 mmol/L concentration.Compounds 3a-e,3g and 3h showed promising in vivo anti-inflammatory activity(ranging from 62.25%to 80.93%) in comparison to diclofenac sodium(81.62%).The ulcerogenic liability and lipid peroxidation activity of these compounds were observed to be less in comparison to diclofenac sodium.These compounds also potently inhibited the lipopolysaccharide(LPS)-induced TNF-αrelease in mice(ID_(50) of 3a-c = 19.98,11.32 and 9.67 mg/kg,respectively).Among the screened compounds,derivative 3c was found to be the most potent and its binding mode within the p38α MAPK is also reported.

Pharmacological potential of Populus nigra extract as antioxidant,anti-inflammatory,cardiovascular and hepatoprotective agent

Objective:To evaluate antioxidant,anti-inflammatory,hepatoprotective and vasorelaxant activities of Pupulus nigra flower buds ethanolic extract.Methods:Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema.Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections.Vasorelaxant effect was estimated in endothelium-intact and-nibbed rings of porcine coronary arteries precontracted with high concentration of U466I9.Results:The results showed a moderate antioxidant activity(40%),but potent anti-inflammatory activity(49.9%)on carrageenan-induced mice paw edema,and also as revealed by histopathologic examination,complete protection against AlCl_3-induced hepatic toxicity.Relaxant effects of the same exlracl on vascular preparation from porcine aorta precontracted with high concentration of U466I9 were considerable at 10^(-1)g/L,and comparable(P>0.05)between endothelium-intact(67.74%,IC_(50)0.04 mg/ml.)and-rubbed(72.72%,IC_(50)=0.075 mg/ml,)aortic rings.Conclusions:The extract exerted significant anti-inflammatory,hepatoprotective and vasorelaxant activities,the latter being cndothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties,probably related to an inhibition of Ca^(2+)influx.

Synthesis and pharmacological properties of naturally occurring prenylated and pyranochalcones as potent anti-inflammatory agents

An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.

Design and Synthesis of Some Enaminonitrile Derivatives of Antipyrine as Potential Novel Anti-Inflammatory and Analgesic Agents

The starting (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)carbon-hydrazonoyl dicyanide (2) was used as a key intermediate for the syntheses of novel acyclic enaminonitriles 3-10. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, 1H NMR, 13C NMR and mass spectra). The anti-inflammatory activity data indicated that many of tested compounds protected rats from carrageenan-induced inflammation, and tested compounds 3, 4, 9 and 10 were the most potent among tested compounds. The analgesic activity was determined by the hot plate test (central analgesic activity) and acetic acid induced writhing assay. The results revealed that compounds 3, 4, 9, and 10 exhibited significant activity. However, compound 10 proved to have better or equivalent activities in comparison to the reference drug.