Developmental perspectives of the drugs targeting enzyme-instigated inflammation: a mini review

Prasher, Parteek; Mudila, Harish; Sharma, Mousmee; Khati, Beena

doi:10.1007/s00044-019-02315-7

Cited by 16 publications

(17 citation statements)

References 243 publications

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“…Under inflammatory conditions, AA is released through the action of PLA 2 upon the membrane phospholipids, being further metabolized via several different enzymatic machineries, namely the LOX and COX pathways, giving rise to a group of pro-inflammatory mediators called eicosanoids [23]. The eicosanoid production is considerably increased during inflammation, with leukotrienes and prostaglandins being products of LOX and COX activity, respectively [25,26]. In regard to COX, there are distinct isoforms such as COX-1, which is constitutively expressed in a variety of cell types being involved in their homeostasis, and the inducible isoform, COX-2, with a specific tissue distribution, thus constituting the most relevant target of anti-inflammatory drugs [26,27,28].…”

Section: Resultsmentioning

confidence: 99%

“…The eicosanoid production is considerably increased during inflammation, with leukotrienes and prostaglandins being products of LOX and COX activity, respectively [25,26]. In regard to COX, there are distinct isoforms such as COX-1, which is constitutively expressed in a variety of cell types being involved in their homeostasis, and the inducible isoform, COX-2, with a specific tissue distribution, thus constituting the most relevant target of anti-inflammatory drugs [26,27,28]. Therefore, we evaluated the ability of EnP(5,8) to inhibit the above-mentioned enzymes, at non-cytotoxic concentrations.…”

Section: Resultsmentioning

confidence: 99%

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Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Pereira

Jiménez

et al. 2019

Marine Drugs

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Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Pereira

Jiménez

et al. 2019

Marine Drugs

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“…Foi descoberto que este metabólito pode ainda atuar no sistema endocanabinoide que, juntamente com a COX-1 e TRPV1, está presente Figura 6. Esquema representativo da lesão tecidual, alteração da estrutura de membrana e instalação e progressão do processo inflamatório, com a transformação de células de defesa e produção de mediadores inflamatórios [1][2]33 em vias modulatórias da dor e de termorregulação, sugerindo ser este um mecanismo mais provável de ação analgésica e antipirética do paracetamol. 37,38 Outros estudos sugerem que outros fármacos, como a dipirona, possam atuar sobre a COX-3 e que este represente o mecanismo preferencial de seus efeitos analgésicos e antitérmicos, embora seja ainda controverso.…”

Section: Eicosanoides: Prostaglandinas Leucotrienos E Tromboxanosunclassified

“…[36][37][38][39] De todas as prostaglandinas conhecidas, a PGE2, PGI2 (prostaciclina), PGD2 e PGF2α (Figura 7) são particularmente relevantes pelo seu papel na inflamação. 33 A produção destes prostanoides é onipresente nos tecidos, mas são especialmente abundantes nos sítios de inflamação, agindo como mediadores lipídicos autócrinos (atuando na própria célula produtora) e parácrinos (atuando em células próximas), visando manter a homeostase local. [40][41] Os tromboxanos (TX) são eicosanoides que, estruturalmente, resultam da substituição do anel ciclopentano encontrado nas prostaglandinas por um anel oxano de seis membros.…”

Section: Eicosanoides: Prostaglandinas Leucotrienos E Tromboxanosunclassified

Pathophysiological Aspects of Inflammation and Drug Design: an Updated Overview

Etienne¹,

Viegas²,

Viegas³

2021

Rev. Virtual Quim.

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Inflammation is a natural response of the organism to damage, injury or tissue lesions caused by foreign matter, trauma, infection, immune reactions and tissue necrosis. As being a protection response, inflammation onset and progression involve immune cells, blood vessels and a number of molecular mediators. Once the inflammatory process begins, it is associated to the release of chemical substances, such as cytokines and chemokines (e.g. TNF-α, lipoxynes, kinins, prostaglandins, leukotrienes) and cellular signaling proteins in the tissue environment and migration cells. As a result of a wealth knowledge through decades of research in fields like physiology, pharmacology and molecular biology, since 1980's a more comprehensive vision emerges, recognizing the inflammatory process as a complex result of an interconnected biochemical and cellular events, acting as a driving force associated to many chronic diseases, including obesity, diabetes, arteriosclerosis, cancer and neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's diseases (AD), responsible by severe social-economic impacts in population worldwide. During the last decades, the therapeutics and research of new drugs have been focused on the search and development of lower toxic non-steroidal anti-inflammatory agents, that could act mainly towards the arachidonic acid cascade, more specifically in the inhibition of COX-1, COX-2 and 5-LOX enzymes and modulating the production of prostaglandins, thromboxane and leukotrienes. More recently, the urge of more efficient, low toxic and more specific drugs to certain inflammatory conditions has directing the research for the development of novel drugs capable to act towards other inflammatory mediators, such as interleukins, TNF-α, nitric oxide, kinase proteins, PPARs, endocannabinoid system, opioid receptors and proteins related to apoptosis, leading to the discovery of new drug candidates with different mechanisms of action, could also act in multiple inflammatory targets. A inflamação é uma reação natural do organismo a danos, injúria ou lesões teciduais devidas à presença de um corpo estranho, trauma, infecções, reações imunológicas e necrose tecidual. Por ser uma resposta protetora, a instalação e progressão da inflamação envolve células imunes, vasos sanguíneos e uma série de mediadores moleculares. Uma vez iniciado, o processo inflamatório está associado à liberação de substâncias químicas como as citocinas e quimiocinas (e.g. TNF-α, lipoxinas, cininas, prostaglandinas, leucotrienos) e proteínas de sinalização celular no ambiente tecidual e células migratórias. Como resultado de um vasto conhecimento acumulado em áreas como a fisiologia, farmacologia e biologia molecular, a partir da década de 1980 surge uma visão mais abrangente do processo inflamatório, passando a reconhecê-lo como decorrente de uma complexa rede eventos bioquímicos e celulares interconectados, atuando como força motriz associada a várias doenças crônicas, incluindo a obesidade, diabetes, arteriosclerose, câncer e distúrbio...

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“…The resulting prostaglandins and leukotrienes mediate physiological inflammatory responses ranging from physical symptoms to severe diseased conditions such as arthritis, arteriosclerosis, and cancers (Singh, Prasher, Dhillon, & Bhatti, 2015). The representative anti‐inflammatory chemotherapy based on NSAIDs (nonsteroidal anti‐inflammatory drugs) and COXIBs (selective COX‐2 inhibitors) faced considerable setbacks, hence necessitating the development of novel pharmaceuticals for targeting enzyme‐mediated inflammation (Prasher, Mudila, Sharma, & Khati, 2019). Singh et al developed novel triazine based hybrid molecules for capping enzyme‐instigated inflammation.…”

Section: Anti‐inflammatory Activity Of 135‐triazine Based Hybrid Momentioning

confidence: 99%

Hybrid molecules based on 1,3,5‐triazine as potential therapeutics: A focused review

Prasher

Sharma

Aljabali

et al. 2020

Drug Development Research

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Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux‐pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5‐triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5‐triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5‐triazine based hybrid molecules in the development of pharmaceuticals.

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Developmental perspectives of the drugs targeting enzyme-instigated inflammation: a mini review

Cited by 16 publications

References 243 publications

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Pathophysiological Aspects of Inflammation and Drug Design: an Updated Overview

Hybrid molecules based on 1,3,5‐triazine as potential therapeutics: A focused review

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