Novel N -bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

• Published in: Future medicinal chemistry 2021-10, Vol.13 (20), p.1743-1766
• Main Authors: El Azab, Islam H, Saied, Essa M, Osman, Alaa A, Mehana, Amir E, Saad, Hosam A, Elkanzi, Nadia Aa
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bridged-Ring Compounds - chemical synthesis; Bridged-Ring Compounds - chemistry; Bridged-Ring Compounds - pharmacology; Cell Proliferation - drug effects; Drug Design; Drug Screening Assays, Antitumor; Humans; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinases - metabolism; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Tumor Cells, Cultured
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2021-0066

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel -bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated against different human cancer cell lines. Among the identified compounds, compound showed potent anticancer activity against the examined cancer cell lines. The molecular docking study revealed that compound possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.