Thiohydantoin derivatives incorporating a pyrazole core: Design, synthesis and biological evaluation as dual inhibitors of topoisomerase-I and cycloxygenase-2 with anti-cancer and anti-inflammatory activities

Abdellatif, Khaled R.A.; Fadaly, Wael A.A.; Mostafa, Yaser A.; Zaher, Dana M.; Omar, Hany A.

doi:10.1016/j.bioorg.2019.103132

Cited by 42 publications

(32 citation statements)

References 31 publications

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“…Through hydrophobic interaction, the aryl substituent at position 5 interacts with the hydrophobic side-chains of the amino acids Leu368, Leu414, Ile415 and Phe421. In addition, Pyrazole-linked thiohydantoin derivatives 23 were synthesized and tested for their anti-cancer and anti-inflammatory activities [76]. Among them, the nitro substituted compound 23a showed high anti-inflammatory activity (IC50 = 0.65 M) against the COX-2 enzyme as compared with celecoxib (IC50 = 0.84 M) (Figure 27).…”

Section: Pyrazolesmentioning

confidence: 99%

“…In addition to that, a series of compounds were evaluated for their cytotoxic activity against lung carcinoma (A-549), colon (HCT-116) and breast (MCF-7) cancer cell lines. The same compound 23a exhibited the Pyrazole-linked thiohydantoin derivatives 23 were synthesized and tested for their anti-cancer and anti-inflammatory activities [76]. Among them, the nitro substituted compound 23a showed high anti-inflammatory activity (IC 50 = 0.65 µM) against the COX-2 enzyme as compared with celecoxib (IC 50 = 0.84 µM) ( Figure 27).…”

Section: Pyrazolesmentioning

confidence: 99%

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A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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Section: Pyrazolesmentioning

confidence: 99%

Section: Pyrazolesmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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“…The pyrazole derivative–enzyme interaction has been evaluated using molecular docking. The result of this assessment provides the affinity of designed compounds and contributes to the detection of acceptable inhibitors of COX‐2 ( 15 ; 17 ; 23–32 ; 34–37 ; 39 ; 51 ; 58 ; 60 ; 61 ; 69–72 ; 74 ; 85–87 ) [18,26,27–34,35–39] and 5‐LOX ( 46 ; 63 ; 82–84 ) [40–42] catalytic activity. The energy score of docked derivatives appears related to the degree of enzyme inhibition and selectivity.…”

Section: Preclinical and Mechanistic Studies Of Pyrazoles Derivativesmentioning

confidence: 99%

“…Compound 32 with better enzyme interaction ( E score = −15.00 Kcal/mol) possess more H‐bond features (Arg499, Ser516, Gln178, and Tyr341) than other derivatives and celecoxib ( 5 ) [26]. The amino acid residues Phe504, Tyr371, Tyr355, Ser516, His372 Lys197, Trp373, Leu338, His337, and His175 are additional sites accessible to pyrazole derivatives [32–36]. The compound 74 and some NSAIDs interact with the catalytic (Ser530), ligand‐stabilizing (Arg120), and cavity‐forming (Ile523 and Ala527) residues of COX‐1 that are related to their potency [39].…”

Section: Preclinical and Mechanistic Studies Of Pyrazoles Derivativesmentioning

confidence: 99%

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Development of pyrazole derivatives in the management of inflammation

Turones

Martins

Moreira

et al. 2020

Fundamemntal Clinical Pharma

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The therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis of the first pyrazole—antipyrine in 1887, several other derivatives have been screened for anti‐inflammatory, analgesic, and antipyretic activities. Arguably, the pyrazole ring, as a major pharmacophore and central scaffold partly, defines the pharmacological profile of several derivatives. In this review, we explore the structural–activity relationship that accounts for the pharmacological profile of pyrazole derivatives and highlights future research perspectives capable of optimizing current advancement in the search for safe and efficacy anti‐inflammatory drugs. The flourishing research into the pyrazole derivatives as drug candidates has advanced our understanding of inflammation‐related diseases and treatment.

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Recent advances in the development of celecoxib analogs as anticancer agents: A review

Abdelhaleem

Kassab

El‐Nassan

et al. 2022

Archiv der Pharmazie

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Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) designed to be a selective cyclooxygenase-2 (COX-2) inhibitor. It was approved by the U.S. Food and Drug Administration for the treatment of inflammatory diseases such as osteoarthritis and rheumatoid arthritis. Additionally, celecoxib demonstrated potent antitumor and chemopreventive effects in vitro, in vivo, and in patients. The mechanism of celecoxib's chemopreventive effect is still not fully identified, but it is assumed to be multifactorial. Celecoxib's anticancer activity has been described both as independent of and dependent on its COX-2 inhibitory activity. The current review summarizes the recent advances published between 2000 and 2022 on the structure-based optimization of celecoxib to develop compounds with promising anticancer activity. The structure-activity relationships of celecoxib analogs are discussed, which may be beneficial in the design and development of novel analogs as potent antiproliferative agents in the future.

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Thiohydantoin derivatives incorporating a pyrazole core: Design, synthesis and biological evaluation as dual inhibitors of topoisomerase-I and cycloxygenase-2 with anti-cancer and anti-inflammatory activities

Cited by 42 publications

References 31 publications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Development of pyrazole derivatives in the management of inflammation

Recent advances in the development of celecoxib analogs as anticancer agents: A review

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