Novel uracil derivatives depicted potential anticancer agents: In Vitro, molecular docking, and ADME study

El‐Kalyoubi, Samar; Agili, Fatimah; Adel, Islam; Tantawy, Mohamed A.

doi:10.1016/j.arabjc.2021.103669

Cited by 20 publications

(16 citation statements)

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“…Scheme 1 depicts the synthetic route used to synthesize purine-based derivatives 5a – e . In situ, nitrosation of 6-amino-1-alkyluracils 1a – f [ 21 , 26 , 27 ] with HNO 2 afforded compounds 2a – f in high yields, which were then reduced with ammonium sulphide to produce 5,6-diaminouracils 3a – f . The nucleophilic attack of the amino group of diaminouracils 3a – e on the carbonyl group of 2,7-dibromo-9 H -fluoren-9-one ( 4 ) takes place to form intermediate VII followed by the elimination of a water molecule to form intermediate VIII ( Scheme 2 ), which underwent intramolecular aza-Michael addition that resulted in the formation of compounds 5a – e in reasonable yields (59–68%).…”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAFV600E

et al. 2023

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The investigation of novel EGFR and BRAFV600E dual inhibitors is intended to serve as targeted cancer treatment. Two sets of purine/pteridine-based derivatives were designed and synthesized as EGFR/BRAFV600E dual inhibitors. The majority of the compounds exhibited promising antiproliferative activity on the cancer cell lines tested. Compounds 5a, 5e, and 7e of purine-based and pteridine-based scaffolds were identified as the most potent hits in anti-proliferative screening, with GI50 values of 38 nM, 46 nM, and 44 nM, respectively. Compounds 5a, 5e, and 7e demonstrated promising EGFR inhibitory activity, with IC50 values of 87 nM, 98 nM, and 92 nM, respectively, when compared to erlotinib’s IC50 value of 80 nM. According to the results of the BRAFV600E inhibitory assay, BRAFV600E may not be a viable target for this class of organic compounds. Finally, molecular docking studies were carried out at the EGFR and BRAFV600E active sites to suggest possible binding modes.

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Section: Resultsmentioning

confidence: 99%

“…Compounds 5,6-diaminouracils 3a – f were prepared according to the reported method [ 21 , 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAFV600E

et al. 2023

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“…Anticancer Czito et al [32] Enil uracil against the SARS-CoV-2 with inhibition percentage of 99, 80 and 91 % as compared to the standard drug chloroquine with inhibition percentage of more than 99 % respectively. El-Kalyoubi et al [42] synthesised novel uracil derivatives of the type 29 a-g and El-Kalyoubi et al [43] synthesised a series of target Schiff bases of the type 35 a-c. The reaction involved heating of 5,6-diamino Uracil 33 a-c with 4-dimethylaminobenzaldehyde 34 in acetic acid to yield the desired compounds 35 a-c (Scheme 9).…”

Section: Introductionmentioning

confidence: 99%

“…El‐Kalyoubi et al [42] . synthesised novel uracil derivatives of the type 29 a – g and 32 a – c as Schiff bases of uracil.…”

Section: Introductionmentioning

confidence: 99%

Uracil: A Pharmacophore with Diverse Biological Potential

Jain,

Sharma,

Utreja

2024

ChemistrySelect

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This review article delves into the intricate biological activities of uracil, an essential pyrimidine Base pivotal in RNA structures. Examining its involvement in nucleic acid metabolism, various multifunctional roles, spanning from influencing cell proliferation to its antimicrobial and antiviral properties. The study explores signal transduction pathways affected by uracil, unraveling potential therapeutic applications. By unraveling the nuanced biological mechanisms. This review contributes to a deeper understanding of uracil's impact, offering insights crucial for drug development and advancing biomedical research.

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“…sisplatin), mitotik inhibitörler (ör., paklitaksel), epidermal büyüme faktörü reseptörü (EGFR) inhibitörlerin (örn., gefitinib), VEGF (vasküler endotelyal büyüme faktörü) reseptör inhibitörleri (örneğin bevacizumab), topoizomeraz inhibitörleri (örn. kampotesinler) yaygın olarak kullanılan antikanser ilaçlardır [5].…”

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Synthesis, Characterization, Antioxidant, and Anticancer Studies of Benzimidazole-Thiadiazole Derivatives

Bostancı

Çevik

2022

Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi

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Çalışmamızda yeni antikanser ilaçlar geliştirmek üzere bazı benzimidazol-tiyadiazol türevi bileşikler tasarlanmış ve yapıları 1H-NMR,13C-NMR ve elemental analiz spektral verileriyle kanıtlanmıştır. Bileşiklerin sitotoksik aktiviteleri HT29 hücre hattı üzerinde MTT yöntemi kullanılarak referans bileşik florourasilile kıyaslanarak değerlendirilmiştir. Ayrıca, bileşiklerin seçiciliklerini tespit etmek amacıyla L929 (sağlıklı fare fibroblast hücresi) hücre hattına karşı sitotoksik etkisi değerlendirilmiştir. Bileşiklerin IC50 değerleri incelendiğinde, 5-(2-(2,6-dimetoksifenil)-1H-benz[d]imidazol-5(6)-il)-N-siklohekzil-1,3,4-tiyadiazol-2-amin yapısına sahip BT-2 bileşiği 34,13±2,48 µM IC50 değeri ile referans ilaç fluorourasil (12,84 ± 3,66 µM) ile kıyaslanabilir etki göstermiştir. BT-2 bileşiğinin L929 sağlıklı hücre hattı üzerindeki sitotoksik etkisinin referans ilaçtan daha düşük olduğu tespit edilmiştir. Bu sonuçlar, BT-2 bileşiğinin antikanser etkisinin geliştirilebilmesi konusunda umut vericidir. Ayrıca, TAS ve TOS ile bileşiklerin antioksidan özellikleri değerlendirilmiştir. BT-2 bileşiğinin TOS değerinin kontrol ilaçla karşılaştırılabilir düzeyde olduğu görülmüştür.

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Novel uracil derivatives depicted potential anticancer agents: In Vitro, molecular docking, and ADME study

Cited by 20 publications

References 59 publications

Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAFV600E

Design, Synthesis, and Anti-Proliferative Action of Purine/Pteridine-Based Derivatives as Dual Inhibitors of EGFR and BRAFV600E

Uracil: A Pharmacophore with Diverse Biological Potential

Synthesis, Characterization, Antioxidant, and Anticancer Studies of Benzimidazole-Thiadiazole Derivatives

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