Twenty-five seco-4-methyl-DCK derivatives were designed, synthesized and evaluated for chemoreversal activity when combined with paclitaxel or vincristine in two drug-resistant cancer cell lines (A2780/T and KB-V) respectively. Most of the new compounds displayed moderate to significant MDR reversal activities in the P-gp overexpressing A2780/T and KB-V cells. Especially, compounds 7o and 7y showed the most potent chemosensitization activities with more than 496 and 735 reversal ratios at a concentration of 10 μM. Unexpectedly the newly synthesized compounds did not show chemosensitization activities observed in a non-P-gp overexpressing cisplatin resistant human ovarian cancer cell line (A2780/CDDP), implying that the MDR reversal effects might be associated with P-gp overexpression. Moreover, these compounds did not exhibit significant antiproliferative activities against nontumorigenic cell lines (HUVEC, HOSEC and T29) compared to the positive control verapamil at the tested concentration, which suggested better safety than verapamil. The pharmacological actions of the compounds will be studied further to explore their merit for development as novel candidates to overcome P-gp mediated MDR cancer.

当与紫杉醇或长春新碱联合用于两种耐药性癌细胞系（A2780 / T和KB-V）时，设计，合成并评估了25种seco-4-methyl-DCK衍生物的化学趋化活性。大多数新化合物在过表达P-gp的A2780 / T和KB-V细胞中显示中等至重要的MDR逆转活性。特别是化合物7o和7y在10μM的浓度下，显示出最有效的化学增敏活性，具有超过496和735的逆转比。出乎意料的是，新合成的化合物未显示出在非P-gp过表达的顺铂耐药人类卵巢癌细胞系（A2780 / CDDP）中观察到的化学增敏活性，这意味着MDR逆转作用可能与P-gp过表达有关。此外，与测试浓度的阳性对照维拉帕米相比，这些化合物对非致瘤细胞系（HUVEC，HOSEC和T29）没有显示出显着的抗增殖活性，这表明其安全性优于维拉帕米。将进一步研究这些化合物的药理作用，以探索其作为克服P-gp介导的MDR癌症的新候选药物的开发价值。