New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies

Alamshany, Zahra M.; Algamdi, Eman M.; Othman, Ismail M.M.; Anwar, Manal M.; Nossier, Eman S.

doi:10.1039/d3ra01931d

Cited by 17 publications

(3 citation statements)

References 70 publications

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“…Investigating the absorption, distribution, metabolism, and excretion (ADME) is a critical first step in selecting the best candidates. SwissADME, a free online tool, was used for prediction of the best two compounds’ ADME characteristics [ 48 , 49 , 50 ]. Veber’s rule (molecule with number of rotatable bonds ≤ 10, TPSA ≤ 140 Å 2 ) and Lipinski’s rule (MW ≤ 500, MLogP ≤ 4.15, number of hydrogen bond acceptors ≤ 10 and number of hydrogen bond donors ≤ 5) should be taken into consideration while selecting an oral drug.…”

Section: Methodsmentioning

confidence: 99%

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine Derivatives

Elsenbawy,

Alshehri,

Babteen

et al. 2024

Molecules

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A new series of thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines was designed and synthesized using readily available starting materials, specifically, β-enaminoester. Their cytotoxicity was screened against three cancer cell lines, namely, MCF-7, HCT-116, and PC-3. 2-(4-bromophenyl)triazole 10b and 2-(anthracen-9-yl)triazole 10e afforded excellent potency against MCF-7 cell lines (IC50 = 19.4 ± 0.22 and 14.5 ± 0.30 μM, respectively) compared with doxorubicin (IC50 = 40.0 ± 3.9 μM). The latter derivatives 10b and 10e were further subjected to in silico ADME and docking simulation studies against EGFR and PI3K and could serve as ideal leads for additional modification in the field of anticancer research.

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Section: Methodsmentioning

confidence: 99%

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine Derivatives

Elsenbawy,

Alshehri,

Babteen

et al. 2024

Molecules

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“…On this basis, c-Met is considered a promising target for cancer therapy. 31,128,129 In the same manner, special attention has been paid to TRxR, a Se-dependent enzyme, as it is part of the antioxidant systems in cellular physiology. A great number of scientific reports have described the potent anticancer properties of numerous TRxR inhibitors through the promotion of apoptosis.…”

Section: Cytarabinementioning

confidence: 99%

“…This oncogenic transmembrane receptor tyrosine kinase (RTK) is overexpressed or mutated in several cancer cell lines such as hepatocellular carcinoma (HCC). On this basis, c-Met is considered a promising target for cancer therapy. ,, In the same manner, special attention has been paid to TRxR, a Se-dependent enzyme, as it is part of the antioxidant systems in cellular physiology. A great number of scientific reports have described the potent anticancer properties of numerous TRxR inhibitors through the promotion of apoptosis. ,, Furthermore, this enzyme is notably upregulated in HCC and is involved in cancer progression .…”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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A versatile precursor for one‐pot synthesis of novel azo‐thiazole and thiazole scaffolds as prospective antimicrobial and antioxidant agents

Alamshany,

Tashkandi,

Othman

2024

J Chinese Chemical Soc

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In this study, we present a simple method for preparing a new series of thiazoles with excellent isolated yields. To synthesize the target thiazole scaffolds, a straightforward one‐pot procedure was developed including an amine‐mediated reaction of isoxazolethiazolidin‐4‐one derivative, thiosemicarbazide, and appropriate hydrazonyl chlorides. The reaction conditions for this one‐pot protocol were optimized by experimenting with different solvents and amines. The best results were achieved by conducting the reaction in dioxane with triethylamine at 100°C for 5 h. The structures of the desired products were proved by different elemental analyses and spectral data. Additionally, the antimicrobial efficacy of all target derivatives was assessed against various types of microorganisms. The results observed indicated that the antimicrobial activity of the thiosemicarbazone derivative 2 was the strongest activity among the new series, with MIC values ranging from 0.03 ± 0.01 to 0.98 ± 0.15 μg/mL. Moreover, antioxidant evaluations were conducted on all the desired targets, using ascorbic acid as a reference drug. Significantly, derivatives 2 and 10 demonstrated the most promising antioxidant inhibitory effects. Additionally, further toxicity studies were performed on the most active novel compounds, revealing their best drug‐like properties and varying toxicity risks in humans.

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New pyrazolopyridine and pyrazolothiazole-based compounds as anti-proliferative agents targeting c-Met kinase inhibition: design, synthesis, biological evaluation, and computational studies

Abstract: c-Met tyrosine kinase plays a key role in the oncogenic process.

Cited by 17 publications

References 70 publications

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine Derivatives

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine Derivatives

Selenization of Small Molecule Drugs: A New Player on the Board

A versatile precursor for one‐pot synthesis of novel azo‐thiazole and thiazole scaffolds as prospective antimicrobial and antioxidant agents

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