New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies

Fadaly, Wael A.A.; Elshaier, Yaseen A.M.M.; Hassanein, Emad H.M.; Abdellatif, Khaled R.A.

doi:10.1016/j.bioorg.2020.103752

Cited by 63 publications

(30 citation statements)

References 93 publications

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“…The hunt for new analogs with desirable pharmacological profiles is a never-ending task in drug discovery programs. With the available literature on pyrazole analogs ( Fadaly et al, 2020 ; Mohamed et al, 2020 ; Azimi et al, 2021 ; Faudzi et al, 2021 ; Verma et al, 2021 ), it is relatively easy for medicinal chemists to proceed with rational synthesis or modification capable of enhancing biological activities. The substitutions, additions, or removal of functional groups are effective strategies for designing biologically important analogs.…”

Section: Final Considerations and Future Perspectivementioning

confidence: 99%

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

et al. 2021

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Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.

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Section: Final Considerations and Future Perspectivementioning

confidence: 99%

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

et al. 2021

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“…The in silico molecular docking analysis confirmed that the 1,2,4‐triazole nucleus acts as the central core nucleus, and not the pyrazole nucleus for imparting the ideal “Y” shape structure to the test compounds in order to achieve selective COX‐2 inhibition. In addition to imparting the GI safety, the internal oxime moiety displays cyclic hydrogen‐bonding interactions thereby stabilizing the test compounds in the COX‐2 active site (Fadaly, Elshaier, Hassanein, & Abdellatif, 2020).…”

Section: Selective Cox‐2 Inhibitors Based On Azole Nucleusmentioning

confidence: 99%

“…N The presence of the numerous binding interactions between the functional groups on test compounds and the active site residues lining the COX-2 isoenzyme resulted in the inhibition of the latter (Elzahhar et al, 2020).…”

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confidence: 99%

“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Prasher

Sharma

2020

Drug Development Research

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An over‐expression of COX‐2 isoenzyme belonging to the Cyclooxygenase Enzyme Family triggers the overproduction of pro‐inflammatory prostaglandins that instigate the development of chronic inflammation and related disorders. Hence, the rationally designed drugs for mitigating over‐activity of COX‐2 isoenzyme play a regulatory role toward the alleviation of the progression of these disorders. However, a selective COX‐2 inhibition chemotherapy prompts several side effects that necessitate the identification of novel molecular scaffolds for deliberating state‐of‐the‐art drug designing strategies. The heterocyclic “azole” scaffold, being polar and hydrophilic, possesses remarkable physicochemical advantages for designing physiologically active molecules capable of interacting with a wide range of biological components, including enzymes, peptides, and metabolites. The substituted derivatives of azole nuclei enable a comprehensive SAR analysis for the appraisal of bioactive profile of the deliberated molecules for obtaining the rationally designed compounds with prominent activities. The comprehensive SAR analysis readily prompted the identification of Y‐shaped molecules and the eminence of bulkier group for COX‐2 selective inhibition. This review presents an epigrammatic collation of the pharmacophore‐profile of the chemotherapeutics based on azole motif for a selective targeting of the COX‐2 isoenzyme.

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“…1,2,4-Triazoles are versatile scaffolds in the synthesis of molecular hybrids, and 1,2,4-triazole clubbed heterocycles exhibit enhanced biological activities comparable with the parent moieties, and therefore have greater applications in medicinal chemistry [21]. For instance, the fused 1,2,4-triazole-imidazolidines possess the enhanced anti-proliferative, and HDAC-tubulin inhibitor [22], isonicotinic acid tethered phenacyl triazoles show anticonvulsant [23], S,N-bis(acyclonucleoside) derivatives exhibit anti-tubercular [24], Cox-2 inhibitor [25], properties. Coumarin tethered pyrazole-oxadiazole hybrids show improved antimicrobial and antioxidant activities [26], for instance, Naproxen analogs of 1,2,4-triazole-5-thiones show potential antinociceptive and anti-inflammatory [27], triazolo [4,3-b] [1,2,4] triazepine-8(9H)-ones have α-amylase and α-glucosidase inhibitory [28], and 4-amino-1,2,4-triazole-Schiff's bases exhibit good anti-diabetic [29], activities.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

Basappa

Vivek²,

Kumara

et al. 2020

Heliyon

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The current study demonstrates the synthesis of coumarin-triazole hybrids 8 (a-e) in four steps starting from substituted salicylaldehyde 1 (a-e), and diethyl malonate 2. The spectroscopic studies provide the structure proofs of the new compounds, and the molecular structure of an intermediate 3a by crystallographic studies. The crystal structure analysis revealed the C-H...O, C-H... π, CO ...π and π...π molecular interactions. Further, the intermolecular interactions were quantified using Hirshfeld surface analysis and the DFT method B3LYP functional with 6-311þþ G (d,p) basis set was employed to optimize the molecular geometry. The synthesized new coumarintriazole hybrids, 8 (a-e) were screened for their α-amylase inhibitory potentials, and the results suggest that amongst the series, compounds 8c, and 8e show the promising inhibition of the enzyme, and might act as lead molecules for anti-diabetic activities. To understand the mode of action in silico molecular docking and ADME screening were performed.

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New 1,2,4-triazole/pyrazole hybrids linked to oxime moiety as nitric oxide donor celecoxib analogs: Synthesis, cyclooxygenase inhibition anti-inflammatory, ulcerogenicity, anti-proliferative activities, apoptosis, molecular modeling and nitric oxide release studies

Cited by 63 publications

References 93 publications

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations

“Azole” as privileged heterocycle for targeting the inducible cyclooxygenase enzyme

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

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