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Discovery of new non-acidic lonazolac analogues with COX-2 selectivity as potent anti-inflammatory agents.

ABSTRACT: Herein, the design and synthesis of some novel 1,3,4-trisubstituted pyrazole derivatives was carried out through the structural modification of lonazolac. All the synthesized compounds were investigated for in vitro COX-1 & COX-2 inhibition and in vivo anti-inflammatory activity by a carrageenan rat paw edema model. Among them, the chalcones 2a and 2b were the most COX-2 selective derivatives (S.I. = 8.22 and 9.31, respectively) and revealed very good in vivo anti-inflammatory potency. Similarly, the compounds 4a, 6b, 7a and 8a exhibited good COX-2 selectivity and in vivo anti-inflammatory activity. The active compounds were selected to further investigate their ulcerogenic activity, and they were found to be less ulcerogenic (ulcer indices = 2.4-8.4) as compared to indomethacin (ulcer index = 17.6) and nearly as ulcerogenic as celecoxib (ulcer index = 8.1). Moreover, histological studies were performed to evaluate the safety of these compounds on the stomach, liver and kidney. Furthermore, a docking study was performed to determine possible binding of the most active compounds 2a and 2b, which showed high docking scores (-9.461 and -7.962 kcal mol-1, respectively) that were comparable to that of celecoxib (-8.692 kcal mol-1).

SUBMITTER: Harras MF

PROVIDER: S-EPMC6844278 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Discovery of new non-acidic lonazolac analogues with COX-2 selectivity as potent anti-inflammatory agents.

Harras Marwa F MF Sabour Rehab R Alkamali Omkulthom Mohamed OM

MedChemComm 20190722 10

Herein, the design and synthesis of some novel 1,3,4-trisubstituted pyrazole derivatives was carried out through the structural modification of lonazolac. All the synthesized compounds were investigated for in vitro COX-1 & COX-2 inhibition and in vivo anti-inflammatory activity by a carrageenan rat paw edema model. Among them, the chalcones 2a and 2b were the most COX-2 selective derivatives (S.I. = 8.22 and 9.31, respectively) and revealed very good in vivo a ...[more]

PMID: 31803395

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Project description:Lectins are defined as carbohydrate-binding proteins/glycoproteins of none immune origin, they are ubiquitous in nature, exist from bacteria to human cells. And due to their carbohydrate-binding recognition capacity, they have been a useful biological tool for the purification of glycoproteins and their subsequent characterization. Some plant lectins have also been revealed to own antinociceptive, antiulcer, and anti-inflammatory properties, where these features, in many instances, depending on the lectin carbohydrate-binding site. Coronavirus disease of 2019 (COVID-19) is a respiratory disease that struck the entire world leaving millions of people dead and more infected. Although COVID-19 vaccines have been made available, and quite a large number of world populations have already been immunized, the viral infection rates remained in acceleration, which continues to provoke major concern about the vaccines' efficacy. The belief in the ineffectiveness of the vaccine has been attributed in part to the recurrent mutations that occur in the epitope determinant fragments of the virus. Coronavirus envelope surface is extensively glycosylated being covered by more than sixty N-linked oligomannose, composite, and hybrid glycans with a core of Man3GlcNAc2Asn. In addition some O-linked glycans are also detected. Of these glyco-chains, many have also been exposed to several mutations, and a few remained conserved. Therefore, numerous plant lectins with a specificity directed towards these viral envelope sugars have been found to interact preferentially with them and are suggested to be scrutinized as a possible future tool to combat coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through blocking the viral attachment to the host cells. In this review, we will discuss the possible applications of plant lectins as anti-coronaviruses including SARS-CoV-2, antinociceptive, anti-inflammatory, and antiulcer agents with the proposed mechanism of their actions.

Dataset Information

Discovery of new non-acidic lonazolac analogues with COX-2 selectivity as potent anti-inflammatory agents.

Publications

Discovery of new non-acidic lonazolac analogues with COX-2 selectivity as potent anti-inflammatory agents.

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