Dei Silvia, Budriesi Roberta, Sudwan Paiwan, Ferraroni Marta, Chiarini Alberto, Garnier-Suillerot Arlette, Manetti Dina, Martelli Cecilia, Scapecchi Serena, Teodori Elisabetta
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Bioorg Med Chem. 2005 Feb 15;13(4):985-98. doi: 10.1016/j.bmc.2004.11.043.
A series of compounds with a diphenylmethyl cyclohexyl skeleton, loosely related to verapamil, has been synthesized and tested as MDR modulators on anthracycline-resistant erythroleukemia K 562 cells. Their residual cardiovascular action (negative inotropic and chronotropic activity as well as vasorelaxant activity) was evaluated on guinea-pig isolated atria preparations and on guinea-pig aortic strip preparations. Most compounds of the series possess a good MDR-reverting activity together with a low cardiovascular action. Among them, compounds 3a1, 7a, and 8a are more potent than verapamil as MDR reverters and lack any cardiovascular action; they can represent useful leads for the development of new safe MDR reversing drugs.
合成了一系列具有二苯甲基环己基骨架、与维拉帕米有松散关联的化合物，并在耐蒽环类抗生素的红白血病K 562细胞上作为多药耐药（MDR）调节剂进行了测试。在豚鼠离体心房制剂和豚鼠主动脉条制剂上评估了它们残留的心血管作用（负性肌力和变时活性以及血管舒张活性）。该系列中的大多数化合物具有良好的MDR逆转活性以及较低的心血管作用。其中，化合物3a1、7a和8a作为MDR逆转剂比维拉帕米更有效，并且没有任何心血管作用；它们可以作为开发新型安全MDR逆转药物的有用先导化合物。
