Design, synthesis and anti-inflammatory activity of diterpenoid alkaloids and non-steroidal anti-inflammatory drug hybrids based on molecular hybridization strategy

Article

Author: Ji, Wan-Sheng ; Shan, Lian-Hai ; Xiao, Yao ; Guo, Ming-Hao ; Zhou, Xian-Li ; Wen, Peng ; Gao, Feng

Mol. hybridization is a widely employed approach in pharmaceutical chem. for modifying drugs with the aim of improving pharmacol. efficacy and reducing adverse effects.A prime example of this is the case of benorylate, which was created by combining aspirin and acetaminophen, two non-steroidal anti-inflammatory drugs (NSAIDs).Diterpenoid alkaloids, which exhibit potent anti-inflammatory activity, have limitations in their application due to their toxicity and side effects.Thus, we aimed to design new anti-inflammatory lead compounds through the mol. hybridization of the anti-inflammatory active skeletons (lappaconitine, aconorine, and bulleyaconitine A) of diterpenoid alkaloids with classical NSAIDs.In this study, we synthesized 25 diterpenoid alkaloid derivatives with NSAIDs, organized into four series.Among these derivatives, lappaconitine derivative 1e demonstrated the strongest inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells with minimal cytotoxicity.Addnl., 1e effectively suppressed the inflammatory response induced by carrageenan in vivo, with a swelling rate of only 1%.This anti-inflammatory potency was found to be significantly superior to that of naproxen.The mol. docking anal. revealed that the binding affinity of 1e was scored as -10.3 kcal/mol, suggesting that it forms a stable complex with cyclooxygenase-2 (COX-2).Therefore, compound 1e holds potential as a lead anti-inflammatory compound that could be further developed.

01 Apr 2022·International Journal of PharmaceuticsQ2 · MEDICINE

Descriptors for some compounds with pharmacological activity; calculation of properties

Q2 · MEDICINE

Article

Author: Acree, William E ; Abraham, Michael H ; Liu, Xiangli

Abraham model solute descriptors have been determined for nisoldipine, nizatidine, loratadine, zonisamide, oxaprozin, rebamipide, domperidone, temozolomide, 'florfenicol', florfenicol A, dapsone, chrysin, benorilate, β-lapachone, and Ipriflavone based on published partition coefficients, molar solubilities and gas chromatographic retention indices. The calculated solute descriptors, combined with our previously published Abraham model correlations, are used to predict several important physicochemical and biological properties, such as air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane and water-skin partition coefficients, as well as permeation from water through skin.

01 Aug 2018·Analytica Chimica ActaQ2 · CHEMISTRY

Fabrication and characterization of metal organic frameworks/ polyvinyl alcohol cryogel and their application in extraction of non-steroidal anti-inflammatory drugs in water samples

Q2 · CHEMISTRY

Article

Author: Yuan, Ming ; Wang, Yudan ; Hou, Xiaohong ; Hu, Qi ; Li, Shuo ; Cui, Jianan ; Wang, Ting ; Zhang, Yang

A series of novel MOFs/PVA composite cryogel (MIL-101(Cr)/PVA, MIL-100(Fe)/PVA, ZIF-8(Zn)/PVA, MOF-199(Cu)/PVA and MIL-53(Al)/PVA) were fabricated by using a facile and green freeze-thaw approach for the first time. MIL-101(Cr)/PVA cryogel was selected as a VA-SPE sorbent for extraction of four NSAIDs in environmental water samples. The procedures of condition investigation (synthesis and extraction optimization) and characterization were also performed. And a satisfactory result of methodology validation was obtained by making use of HPLC-MS/MS. Under the optimum conditions, good sensitivity levels were achieved with the limits of detection between 0.007 and 0.037 μg L^-1, a linearity of 0.10-10 μg L^-1 for phenylbutazone, indomethacin, nimesulide and 0.020-2.0 μg L^-1 for benorilate (r² ≥ 0.9934). The relative recoveries of the target analytes were in the range from 78.44% to 105.7% with relative standard deviation (RSD) from 1.33% to 9.85%. In the extraction process, MIL-101(Cr)/PVA cryogel as a whole sheet outperformed the pristine dispersive MIL-101(Cr) in separation from solvent, and the application of cryogel also simplified the operation procedure. Additionally, the combination of PVA with MOFs might strengthen the interaction ability between the sorbent and analytes. This novel pretreatment method had a variety of merits, such as easy operation, high enrichment efficiency and low matrix effect. It looks forward to further optimization or functionalization and application of these MOFs/PVA cryogel in various disciplines.

100 Deals associated with Benorilate

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KEGG	Wiki	ATC	Drug Bank
D07291	Benorilate	N02BA10	DB13657

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Indication	Country/Location	Organization	Date
Fever	CN	Chengdu Pharmaceutical Co. Ltd.	01 Jan 1981
Pain	CN	Chengdu Pharmaceutical Co. Ltd.	01 Jan 1981

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