Design and synthesis of novel dasatinib derivatives as inhibitors of leukemia stem cells

Li, Huiying; He, Dingdi; Zhao, Xiujuan; Sun, Tong-Yan; Zhang, Quan; Bai, Cui-Gai; Chen, Yue

doi:10.1016/j.bmcl.2018.01.011

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The anticancer activity of the 1,2,3-triazole-tethered dasatinib derivatives were studied in HL60, K562 (leukaemia) and KG1a (leukaemia progenitor) cell lines. 75 Among the triazole-containing lead compounds, 36 ( Fig. 6) showed superior inhibitory activity (IC 50 = 0.14 µM) in the KG1a cell line, following evaluation in MCF-7 and B16BL6 cells using the colony forming and cell wound scratch bioassays, respectively.…”

Section: Diverse 123-triazole-containing Heterocyclic Hybridsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: Diverse 123-triazole-containing Heterocyclic Hybridsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

View full text Add to dashboard Cite

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“…Moving ahead, the author searched the Cortellis Drug Discovery Intelligence platform for “Related Drugs”, using 59 as query, which featured two reports , describing its analogs. Presently, 3 and 4 (Chart ) are in the “Preclinical” phase, whereas others, 60 – 65 (Chart ), are under “Biological Testing”.…”

Section: Synthetic Organic Molecules/nces As Anti-csc Agentsmentioning

confidence: 99%

“…The acrylamide derivatives 62 and 64 were equipotent as 59 . The bioisosteric replacements yielded less potent analogs of 59 in related assays and were less toxic in vivo following single-dose oral administration . To summarize, a simple and effective strategy based on the “active chemical analog” approach for the structural modifications of an established drug was presented for fine-tuning the anticancer and anti-CSC activity.…”

Section: Synthetic Organic Molecules/nces As Anti-csc Agentsmentioning

confidence: 99%

“…110 Previously, Tian et al (2018) convincingly proved that 59 blocked paclitaxel-induced breast CSC enrichment and Src activation in both native and paclitaxel-resistant TNBC cells and enhanced sensitivity to paclitaxel. 111 Moving ahead, the author searched the Cortellis Drug Discovery Intelligence platform for "Related Drugs", using 59 as query, which featured two reports 112,113 describing its analogs. Presently, 3 and 4 (Chart 1) are in the "Preclinical" phase, whereas others, 60−65 (Chart 6), are under "Biological Testing".…”

Section: ■ Drug Repurposing For Csc Targetingmentioning

confidence: 99%

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Cancer Stem Cell (CSC) Inhibitors in Oncology—A Promise for a Better Therapeutic Outcome: State of the Art and Future Perspectives

Kharkar

2020

J. Med. Chem.

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Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal, tumorigenicity, pluripotency, chemoresistance, differentiation, invasive ability, and plasticity, reside in specialized tumor niches and are responsible for tumor maintenance, metastasis, therapy resistance, and tumor relapse. The new-age “hierarchical or CSC” model of tumor heterogeneity is based on the concept of eradicating CSCs to prevent tumor relapse and therapy resistance. Small-molecular entities and biologics acting on various stemness signaling pathways, surface markers, efflux transporters, or components of complex tumor microenvironment are under intense investigation as potential anti-CSC agents. In addition, smart nanotherapeutic tools have proved their utility in achieving CSC targeting. Several CSC inhibitors in clinical development have shown promise, either as mono- or combination therapy, in refractory and difficult-to-treat cancers. Clinical investigations with CSC marker follow-up as a measure of clinical efficacy are needed to turn the “hype” into the “hope” these new-age oncology therapeutics have to offer.

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Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

Yang¹,

Xuan²,

Li³

et al. 2022

Archiv der Pharmazie

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Leukemia, a hematological malignancy originating from the bone marrow, is the principal cancer of childhood. In recent decades, improved remission rates and survival of patients with leukemia have been achieved due to significant breakthroughs in the treatment. However, chemoresistance and relapse are common, creating an urgent need for the search for novel pharmaceutical interventions. 1,2,3‐Triazole is one of the most fascinating pharmacophores in the discovery of new drugs, and several 1,2,3‐triazole derivatives have already been used in clinics or are under clinical evaluation for the treatment of cancers. In particular, 1,2,3‐triazole hybrids could suppress tumor proliferation, invasion, and metastasis by inhibiting enzymes, proteins, and receptors in cancer cells, revealing their potential as putative antileukemic agents. This review covers the recent advances regarding the 1,2,3‐triazole hybrids with potential antileukemic activity, focusing on the chemical structures, structure–activity relationship, and mechanisms of action, covering articles published from January 2017 to January 2022.

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Design and synthesis of novel dasatinib derivatives as inhibitors of leukemia stem cells

Cited by 6 publications

References 16 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Cancer Stem Cell (CSC) Inhibitors in Oncology—A Promise for a Better Therapeutic Outcome: State of the Art and Future Perspectives

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

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