Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids

Abdelall, Eman K. A.; Abdelhamid, Abdou O.

doi:10.1016/j.bmcl.2017.08.023

Cited by 10 publications

(1 citation statement)

References 21 publications

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“…Coxibs have the same diaryl structure with a core ring composed of five members, such as pyrazole, pyridine, oxazole, or oxole, and the previously developed isoxazole, which has shown a positive anti-inflammatory action and a potential specificity for COX-2 ( Abdelall et al, 2017 ). Specifically, the volume of COX-2 is greater than that of COX-1 because of a side pocket that can hold a big aryl.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives

Alam,

Khan,

Saeed Jan

et al. 2023

Front. Chem.

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Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski’s rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.

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Section: Introductionmentioning

confidence: 99%

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives

Alam,

Khan,

Saeed Jan

et al. 2023

Front. Chem.

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An efficient synthesis of novel isoxazole bearing pyrazole derivatives via [3 + 2] heteroannulation using cupric acetate

Audichya¹,

Savant

Naliapara

2021

Journal of Heterocyclic Chem

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The synthesis of novel 3‐(4,5‐dichloro‐2‐fluorophenyl)‐1‐phenyl‐4‐(3‐phenylisoxazol‐5‐yl)‐1H‐pyrazole(7a–p) has been achieved via [3 + 2] heteroannulation reaction 3‐(3‐[4,5‐dichloro‐2‐fluorophenyl]‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1‐phenylprop‐2‐en‐1‐one(6a–p) and hydroxylamine hydro chloride using cupric acetate as homogenous precatalyst. Pyrazole derivatives were prepared by using etidronic acid as catalyst followed by Vilsmeier‐Haack reaction. An efficient green synthesis of isoxazole derivatives bearing pyrazole ring has been demonstrated with excellent yields. Structures of novel isoxazole derivatives were confirmed by elemental analysis and 1H NMR, 13C NMR, Mass, IR spectral studies.

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Pharmacology of Gasotransmitters (Nitric Oxide and Carbon Monoxide) and Their Action

Deshmukh

Harwansh

Bandyopadhyay

et al. 2020

Frontiers in Pharmacology of Neurotransmitters

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Synthesis and biological evaluations of new nitric oxide-anti-inflammatory drug hybrids

Cited by 10 publications

References 21 publications

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives

An efficient synthesis of novel isoxazole bearing pyrazole derivatives via [3 + 2] heteroannulation using cupric acetate

Pharmacology of Gasotransmitters (Nitric Oxide and Carbon Monoxide) and Their Action

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