Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors

Martínez-González, Sonia; Rodríguez-Arístegui, Sonsoles; Oliva, Cristina Gómez de la; Hernández, Ana Isabel; Cantalapiedra, Esther González; Varela, Carmen; García, Ana; Rabal, Obdulia; Oyarzábal, Julen; Bischoff, James R.; Klett, Javier; Albarran, Maria I.; Cebriá, Antonio; Ajenjo, Nuria; García-Serelde, Beatriz; Gómez‐Casero, Elena; Cuadrado-Urbano, Manuel; Cebrián, David; Blanco‐Aparicio, Carmen; Pastor, Joaquı́n

doi:10.1016/j.ejmech.2019.02.022

Cited by 26 publications

(9 citation statements)

References 57 publications

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“…reported synthesis of a series of novel triazolo[4,3- b ]pyridazin-3-yl-quinoline derivatives 57 ( Fig. 10 ) as PIM inhibitors [ 73 ]. Lead optimization techniques identified compound 57q as a selective PIM-1/3 inhibitor (IC 50 : 7 nM/70 nM) and antiproliferative agent against several tumor cells lines with GI 50 values of 1.48–25.4 μM.…”

Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

198

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The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

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Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

198

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“…PIM1/3 kinase activities were measured as previously described in Martínez-Gonzalez et al [49]. HASPIN activity was measured using the commercial ADP GLO assay (Promega), a homogeneous assay measuring ADP accumulation, as a universal product of kinase activity.…”

Section: Kinase Assaysmentioning

confidence: 99%

Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells

Cash

Alcalá

Rico-Ferreira

et al. 2020

Cancers

Self Cite

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Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC.

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“…In enzyme inhibitors; sub‐categories are identified, like kinase inhibitors, topoisomerase inhibitors, methionine aminopeptidase type II inhibitors, aromatase inhibitors, COX inhibitors etc. Few structures of 1,2,4‐triazole having anticancer potential via PIM inhibitor and topoisomerase inhibitors are illustrated in Figure 2 [32,33] …”

Section: Introductionmentioning

confidence: 99%

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

Rathod

Kumar

2022

Chemistry & Biodiversity

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Cancer is still one of the leading causes of death worldwide. Many researchers are working to design and develop heterocyclic-based drugs with the potential to treat cancer at various stages. There is always an unmet need to discover new anticancer drugs to treat different types of cancer. Based on literature reports, it was evident that hybrid 1,2,4-triazoles exhibit a wide spectrum of biological potential (particularly potent anticancer activity), as compared to the corresponding monocyclic compounds. In this review, we summarized fused/hybrid 1,2,4-triazole and poly-functionalized 1,2,4-triazoles as anticancer agents. Triazole may be fused with other heterocyclic scaffolds like pyrimidine, pyridine, piperidine, quinoxaline, quinazoline, thiadiazine, indole, phthalazine etc. A clear explanation of the method of synthesis, structure-activity relationship, and in vitro results plus the inhibitory concentration of new molecules are focused on in this review article.

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Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors

Cited by 26 publications

References 57 publications

An insight on medicinal attributes of 1,2,4-triazoles

An insight on medicinal attributes of 1,2,4-triazoles

Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

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