Thiophene derivative inflicts cytotoxicity via an intrinsic apoptotic pathway on human acute lymphoblastic leukemia cells

• Published in: PloS one 2023-12, Vol.18 (12), p.e0295441-e0295441
• Main Authors: Swain, Risa Mia, Sanchez, Anahi, Gutierrez, Denisse A, Varela-Ramirez, Armando, Aguilera, Renato J
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Anticancer properties; Antineoplastic Agents - pharmacology; Antineoplastic drugs; Antitumor activity; Apoptosis; Biology and Life Sciences; Blood cancer; Cancer; Carbonyl compounds; Carbonyls; Care and treatment; Cell death; Cell Line, Tumor; Cell Proliferation; Cytotoxicity; Depolarization; Diagnosis; Drug Screening Assays, Antitumor; Estrogen receptors; Estrogens; Evaluation; Flow cytometry; Fungicides; Health aspects; Health care disparities; Heterocyclic compounds; High-throughput screening; Humans; Kinases; Leukemia; Libraries; Lymphatic leukemia; Lymphoma; Medicine and Health Sciences; Microorganisms; Mitochondria; Molecular Structure; Non-Hodgkin's lymphomas; Penicillin; Phosphatidylserine; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Reactive oxygen species; Research and Analysis Methods; Scientific equipment and supplies industry; Structure-Activity Relationship; Thiophene; Thiophenes; Thiophenes - pharmacology; Tumor cell lines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0295441

In an effort to identify novel anti-cancer agents, we employed a well-established High Throughput Screening (HTS) assay to assess the cytotoxic effect of compounds within the ChemBridge DIVERSet Library on a lymphoma cell line. This screen revealed a novel thiophene, F8 (methyl 5-[(dimethylamino)carbonyl]-4-methyl-2-[(3-phenyl-2-propynoyl) amino]-3-thiophenecarboxylate), that displays anti-cancer activity on lymphoma, leukemia, and other cancer cell lines. Thiophenes and thiophene derivatives have emerged as an important class of heterocyclic compounds that have displayed favorable drug characteristics. They have been previously reported to exhibit a broad spectrum of properties and varied uses in the field of medicine. In addition, they have proven to be effective drugs in various disease scenarios. They contain anti-inflammatory, anti-anxiety, anti-psychotic, anti-microbial, anti-fungal, estrogen receptor modulating, anti-mitotic, kinase inhibiting and anti-cancer activities, rendering compounds with a thiophene a subject of significant interest in the scientific community. Compound F8 consistently induced cell death at a low micromolar range on a small panel of cancer cell lines after a 48 h period. Further investigation revealed that F8 induced phosphatidylserine externalization, reactive oxygen species generation, mitochondrial depolarization, kinase inhibition, and induces apoptosis. These findings demonstrate that F8 has promising anti-cancer activity.