Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents

• Published in: Bioorganic & medicinal chemistry Vol. 19; no. 16; pp. 4730 - 4738
• Main Authors: Luo, Yin, Qiu, Ke-Ming, Lu, Xiang, Liu, Kai, Fu, Jie, Zhu, Hai-Liang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.08.2011; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Antitubulin polymerization; Binding Sites; Biological and medical sciences; Cell Line, Tumor; Cinnamates - chemistry; Cinnamic acid; colchicine; Computer Simulation; crystal structure; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; General aspects; inhibitory concentration 50; Medical sciences; Melanoma - drug therapy; Mice; Models, Molecular; Molecular docking; Pharmacology. Drug treatments; polymerization; Software; Structure-Activity Relationship; Sulfonamide; Sulfonamides - chemistry; Sulfonamides - pharmacology; Swine; tubulin; Tubulin - chemistry; Tubulin - metabolism; Tubulin Modulators - chemical synthesis; Tubulin Modulators - chemistry; Tubulin Modulators - pharmacology; Antitubulin polymerization; Sulfonamide; Antiproliferative activity; Cinnamic acid; Molecular docking; Antineoplastic agent; Molecular structure; Cytotoxicity; Modeling; Imide; Structure activity relation; Molecular model; Binding mode; Chemical synthesis; Antimitotic; Tumor cell; Rodentia; Benzene derivatives; Melanoma; Antitubulin; X ray diffraction; In vitro; Vertebrata; Mammalia; Cell line; Mouse; Cinnamic acid derivatives; Crystalline structure
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.06.088

A series of cinnamic acyl sulfonamide derivatives have been designed and synthesized, and their biological activities were also evaluated for tubulin inhibitory activity. Compound 10c possessed the most potent biological activity (IC50=0.8μg/mL for B16-F10 and IC50=2.4μg/mL for tubulin). Docking simulation was performed to explore the binding model of compound 10c with tubulin. A series of novel cinnamic acyl sulfonamide derivatives (9a–16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC50 value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent.