Discovery of novel indolyl-1,2,4-triazole hybrids as potent vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors with potential anti-renal cancer activity

Al‐Hussain, Sami A.; Farghaly, Thoraya A.; Zaki, Magdi E. A.; Abdulwahab, Hanan Gaber; Al‐Qurashi, Nadia T.; Muhammad, Zeinab A.

doi:10.1016/j.bioorg.2020.104330

Cited by 44 publications

(27 citation statements)

References 42 publications

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“…Also, 1,2,4-triazole nucleus has been researched for various bioactivities. Al-Hussain and others 117 synthesised indolyl-1,2,4-triazole hybrids and evaluated for their anti-cancer activities. Derivatives 57a , 57b and 58 ( Fig.…”

Section: Indole As Anticancer Drugsmentioning

confidence: 99%

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

Dhiman

Sharma

Singh

2022

Acta Pharmaceutica Sinica B

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Section: Indole As Anticancer Drugsmentioning

confidence: 99%

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

Dhiman

Sharma

Singh

2022

Acta Pharmaceutica Sinica B

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“…1), a thiazole derivative developed by GlaxoSmithKline as a potent and selective B-RAFV600E inhibitor, was approved by FDA in 2013 for the treatment of B-RAFV600E-driven tumors. 19 In the light of these facts and in continuation of our effort toward the discovery of potent anticancer agents, [24][25][26][27][28][29][30][31][32][33][34][35][36] herein, novel thiazole derivatives were designed and synthesized as potent B-RAFV600E kinase inhibitors with potential anticancer activities, based on the clinically-approved B-RAFV600E inhibitor, dabrafenib. The design of our target compounds is illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In the light of these facts and in continuation of our effort toward the discovery of potent anticancer agents, 24–36 herein, novel thiazole derivatives were designed and synthesized as potent B-RAFV600E kinase inhibitors with potential anticancer activities, based on the clinically-approved B-RAFV600E inhibitor, dabrafenib. The design of our target compounds is illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma

et al. 2022

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“…Around 60% of the medications used for cancer treatment are based on heterocyclic moieties [13]. Heterocyclic compounds like pyrimidine [16][17][18][19][20][21][22], phthalazine [23], benzothiazole [24], Benzpyrazoline [25,26], indoline [27][28][29][30][31], benzimidazole [32], phthalazone [33], indole [34,35], quinoline [36,37], quinazoline [38] find application in the treatment of renal cancer. Many synthetic nitrogen heterocycles are extremely relevant to pharmacology and medicine.…”

Section: Introductionmentioning

confidence: 99%

ADMET Prediction of synthesized Heterocyclic derivatives to treat renal cancer

Cordeiro¹,

Khan²,

Tajir³

et al. 2022

German J. Pharm. Biomaterials

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A library of 121 potent, synthesized, and characterized compounds from different heterocyclic derivatives such as pyrimidine, phthalazine, benzothiazole, benzpyrazoline, indoline, benzimidazole, phthalazine, indole, quinoline, quinazoline were selected based on their anti-renal cancer activity. The Drug likeness, Bioactivity, Absorption, Distribution, Metabolism, Excretion, and Toxicity of all the screened compounds were predicted through Molinspiration, PreADMET, and Osiris software. After screening 121 compounds, 19 compounds showed drug-like properties and an absorption percentage better than the standard drug Sorafenib. These compounds were further assessed based on their distribution parameter and the compounds that showed plasma protein binding equal to or below 90% and blood-brain barrier penetration below 1.000 were selected, i.e., compounds 3, 23, 64, 65 were then further assessed for the toxicity. Osiris property explorer was used to predict drug relevance and toxicity of the synthesized compounds. Compounds 3 and 23 were non-toxic similar to the standard drug Sorafenib. Compounds 3 and 23 were found to be active as Kinase Inhibitors, with a bioactivity score of 0.2 and 0.6 compared to standard drug sorafenib, which scored 0.44. Therefore Compound 3 N-(4-fluoro-2-methoxyphenyl)-7-methyl-5,6,7,8tetrahydropyrido [4',3':4,5] thieno[2,3-d] pyrimidin-4-amine and compound 23 1-(4-fluorophenyl)-3methyl-N-phenyl-3a,7a-dihydro-1H-pyrazolo [3,4-d] pyrimidin-4-amine belonging to pyrimidine derivatives were considered as best and suggested to be taken further for preclinical and clinical trials. The pyrimidine derivatives with anti-renal cancer activity can serve as a scaffold for the design of renal cancer targeting agents and motivates the further development of effective and safer compounds.

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Discovery of novel indolyl-1,2,4-triazole hybrids as potent vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors with potential anti-renal cancer activity

Cited by 44 publications

References 42 publications

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma

ADMET Prediction of synthesized Heterocyclic derivatives to treat renal cancer

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