1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      New naphthalene-linked pyrazoline–thiazole hybrids as prominent antilung and antibreast cancer inhibitors

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), pioneer members of the receptor tyrosine kinase subfamily, are frequently mutated and/or overexpressed in several types of human cancers, including nonsmall cell lung cancer (NSCLC) and breast cancer, which are leading causes of cancer-related deaths worldwide. EGFR and HER2-focused anti-NSCLC and antibreast cancer studies encouraged us to search for new potential agents. For this purpose, in the current work, naphthalene-linked pyrazoline–thiazole hybrids ( BTT-110 and BTP-110) were synthesized and examined for their antiproliferative effects on A549 NSCLC and MCF-7 breast cancer cell lines. According to the results, the MTT assay showed that BTT-5 induced strong toxicity in A549 cells with an IC 50 value of 9.51 ± 3.35 μM compared to lapatinib (IC 50 = 16.44 ± 3.92 μM). BTT-5 also presented a high selectivity profile between the Jurkat cell line and PBMCs (healthy) (SI = 65.65). Furthermore, BTT-5 augmented apoptosis significantly in A549 cells (18.40%). BTT-5 displayed significant EGFR inhibition (58.32%) and no significant HER2 inhibition at 10 μM concentration, showing its selective kinase inhibitory effects. The molecular docking assessment indicated that BTT-5 showed high affinity with a different binding profile than lapatinib in the ATP binding cleft of EGFR. Consequently, BTT-5 can serve as a lead for future anti-NSCLC studies.

          Related collections

          Most cited references56

          • Record: found
          • Abstract: found
          • Article: not found

          Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor.

          The crystal structure of the kinase domain from the epidermal growth factor receptor (EGFRK) including forty amino acids from the carboxyl-terminal tail has been determined to 2.6-A resolution, both with and without an EGFRK-specific inhibitor currently in Phase III clinical trials as an anti-cancer agent, erlotinib (OSI-774, CP-358,774, Tarceva(TM)). The EGFR family members are distinguished from all other known receptor tyrosine kinases in possessing constitutive kinase activity without a phosphorylation event within their kinase domains. Despite its lack of phosphorylation, we find that the EGFRK activation loop adopts a conformation similar to that of the phosphorylated active form of the kinase domain from the insulin receptor. Surprisingly, key residues of a putative dimerization motif lying between the EGFRK domain and carboxyl-terminal substrate docking sites are found in close contact with the kinase domain. Significant intermolecular contacts involving the carboxyl-terminal tail are discussed with respect to receptor oligomerization.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            EGFR antagonists in cancer treatment.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Emerging therapeutic agents for advanced non-small cell lung cancer

              Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
                Bookmark

                Author and article information

                Journal
                Turk J Chem
                Turk J Chem
                Turkish Journal of Chemistry
                Scientific and Technological Research Council of Turkey (TUBITAK)
                1300-0527
                1303-6130
                2024
                18 November 2024
                : 48
                : 6
                : 856-866
                Affiliations
                [1 ]Department of Bioengineering Sciences, İzmir Katip Çelebi University, İzmir, Turkiye
                [2 ]Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
                [3 ]Department of Drug Discovery, Science Farm Ltd., Kumamoto, Japan
                [4 ]Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Burdur, Turkiye
                [5 ]Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkiye
                Author notes
                Author information
                https://orcid.org/0000-0002-9796-7669
                https://orcid.org/0000-0002-2968-3939
                https://orcid.org/0000-0001-6705-4052
                https://orcid.org/0000-0003-4847-9711
                Article
                tjc-48-06-856
                10.55730/1300-0527.3704
                11706297
                39780846
                3c39d2af-85da-415a-9973-0618e43a11ce
                © TÜBİTAK

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 30 August 2024
                : 19 December 2024
                : 18 November 2024
                Funding
                Funded by: The Scientific and Technological Research Council of Türkiye (TÜBİTAK)
                Award ID: 1059B192100113
                This study was supported by The Scientific and Technological Research Council of Türkiye (TÜBİTAK) via grant number 1059B192100113.
                Categories
                Research Article

                naphthalene,pyrazoline,thiazole,epidermal growth factor receptor,nonsmall cell lung cancer,breast cancer

                Comments

                Comment on this article