Design, Synthesis, Molecular Docking, and Tumor Resistance Reversal Activity Evaluation of Matrine Derivative with Thiophene Structure

• Main Authors: Jinrui Wei, Yuehui Liang, Lichuan Wu
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Molecules
• Subjects: nasopharyngeal carcinoma; drug resistance; matrine derivative; molecular docking
• Online Access: https://www.mdpi.com/1420-3049/26/2/417

Nasopharyngeal carcinoma (NPC) frequently occurs in Southern China. The main treatments of NPC are chemotherapy and radiotherapy. However, chemo-resistance arises as a big obstacle in treating NPC. Therefore, there is a great need to develop new compounds that could reverse tumor drug resistance. In this study, eight matrine derivatives containing thiophene group were designed and synthesized. Structures of these 8 compounds were characterized by ¹H-NMR, ¹³C-NMR, and high-resolution mass spectrometer (HRMS). The cytotoxicity and preliminary synergistic effects of these 8 compounds were detected against nasopharyngeal carcinoma (NPC) cells and cisplatin-resistant NPC cells (CNE2/CDDP), respectively. Furthermore, the in vivo and in vitro tumor resistance reversal effects of compound <b>3f</b> were evaluated. Moreover, docking studies were performed in Bclw (2Y6W). The results displayed that compound <b>3f</b> showed synergistic inhibitory effects with cisplatin against CNE2/CDDP cells proliferation via apoptosis induction. Docking results revealed that compound <b>3f</b> may exert its effects via inhibiting anti-apoptosis protein Bcl-w.