New quinoline/1,2,4-triazole hybrids as dual inhibitors of COX-2/5-LOX and inflammatory cytokines: Design, synthesis, and docking study

Mohassab, Aliaa M.; Hassan, Heba A.; Abdelhamid, Dalia; Gouda, Ahmed M.; Gomaa, Hesham A.M.; Youssif, Bahaa G.M.; Radwan, Mohamed O.; Fujita, Mikako; Otsuka, Masami; Abdel‐Aziz, Mohamed

doi:10.1016/j.molstruc.2021.130948

Cited by 21 publications

(10 citation statements)

References 63 publications

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“…Traditional NSAIDs have a multitude of side effects, including gastrointestinal toxicity due to COX-1 inhibition, which is essential for the integrity of the stomach mucosa. COX-2 is an inducible type that is activated when an inflammatory stimulus is present (Abdelazeem et al, 2017;Abdel-Aziz et al, 2022;Abdelrahman & Youssif, 2017;Hendawy et al, 2021;Mohassab et al, 2021;Youssif et al, 2006Youssif et al, , 2019. As a result, the development of new COX-2 selective anti-inflammatory drugs is a hotly disputed research area, Figure 7.…”

Section: Anti-inflammatory Quinazolinesmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of quinazolines

Gomaa

2022

Chem Biol Drug Des

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Quinazoline heterocycles are critical in the development of medications.Quinazoline derivatives have been intensively researched, providing a wide range of compounds with diverse biological roles. The quinazoline nucleus has garnered a lot of attention in medical chemistry in recent years. It was assumed to be a pharmacophore component in the development of physiologically interesting drugs. This review is an attempt to increase the potential of quinazoline by highlighting a wide range of advancements demonstrated by numerous derivatives of the quinazoline moiety, as well as focusing on diverse pharmacological actions of the quinazoline moiety. This review compiles recent studies on the quinazoline moiety described in the literature by researchers.

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Section: Anti-inflammatory Quinazolinesmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of quinazolines

Gomaa

2022

Chem Biol Drug Des

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“…Because of their wide spectrum of biological properties, quinoline derivatives with a fused heterocyclic structure have piqued the interest of chemists and biologists. [37][38][39] By conjugating a quinoline scaffold with the 1,2,4-oxadiazole ring, a set of 1,2, 4-oxadiazole quinolone-functionalized derivatives was developed.…”

Section: Antitumor Agentsmentioning

confidence: 99%

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

Hendawy

2022

Archiv der Pharmazie

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Nitrogen heterocycles play an essential role in medication development. The 1,2,4‐oxadiazole heterocycle has been extensively studied, yielding a large variety of molecules with varied biological functions. The 1,2,4‐oxadiazole shows bioisosteric equivalency with ester and amide moieties. In recent years, the 1,2,4‐oxadiazole nucleus has received a lot of attention in medicinal chemistry. It was thought to be a pharmacophore component in the production of biologically intriguing drugs. This review presents a comprehensive overview of the recent achievements in the biological activities of 1,2,4‐oxadiazoles as potential antimicrobial, anticancer, anti‐inflammatory, neuroprotective, and antidiabetic agents. The structure–activity relationship and mechanisms of action are also reviewed.

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“…The docking study was performed into the crystal structure of COX-1 (pdb 1EQG) [43] and COX-2 (pdb 1CX2) [44] using AutoDock 4.2 [45]. The ligands (8a,e,f) and protein molecules were prepared into the suitable formate (pdbqt) for AutoDock following the previous report [46]. In the current study, COX-1/2 proteins were used as rigid molecules, while the ligands were docked as flexible molecules.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

“…AutoDock 4.2 [45] was used to dock the test compounds into the active sites of the two COXs. The study was performed following the previous report [46]. The generated 2/3D figures of the binding modes of the test compounds were created by discovery studio visualizer [47].…”

Section: Annexin V-fitc/pi Apoptosis Assaymentioning

confidence: 99%

Pyrrolizine/Indolizine-NSAID Hybrids: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

et al. 2021

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In the current study, eight new hybrids of the NSAIDs, ibuprofen and ketoprofen with five pyrrolizine/indolizine derivatives were designed and synthesized. The chemical structures of these hybrids were confirmed by spectral and elemental analyses. The antiproliferative activities of these hybrids (5 μM) was investigated against MCF-7, A549, and HT-29 cancer cell lines using the cell viability assay, MTT assay. The results revealed 4–71% inhibition of the growth of the three cancer cell lines, where 8a,e,f were the most active. In addition, an investigation of the antiproliferative activity of 8a,e,f against MCF-7 cells revealed IC50 values of 7.61, 1.07, and 3.16 μM, respectively. Cell cycle analysis of MCF-7 cells treated with the three hybrids at 5 μM revealed a pro-apoptotic increase in cells at preG1 and cell cycle arrest at the G1 and S phases. In addition, the three hybrids induced early apoptotic events in MCF-7 cells. The results of the molecular docking of the three hybrids into COX-1/2 revealed higher binding free energies than their parent compounds 5a,c and the co-crystallized ligands, ibuprofen and SC-558. The results also indicated higher binding free energies toward COX-2 over COX-1. Moreover, analysis of the binding modes of 8a,e,f into COX-2 revealed partial superposition with the co-crystallized ligand, SC-558 with the formation of essential hydrogen bonds, electrostatic, or hydrophobic interactions with the key amino acid His90 and Arg513. The new hybrids also showed drug-likeness scores in the range of 1.06–2.03 compared to ibuprofen (0.65) and ketoprofen (0.57). These results above indicated that compounds 8a,e,f deserve additional investigation as potential anticancer candidates.

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New quinoline/1,2,4-triazole hybrids as dual inhibitors of COX-2/5-LOX and inflammatory cytokines: Design, synthesis, and docking study

Cited by 21 publications

References 63 publications

A comprehensive review of recent advances in the biological activities of quinazolines

A comprehensive review of recent advances in the biological activities of quinazolines

A comprehensive review of recent advances in the biological activities of 1,2,4‐oxadiazoles

Pyrrolizine/Indolizine-NSAID Hybrids: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies

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