A series of novel tetrazole analogues of resveratrol were synthesized and evaluated for their anti-leukemic activity against an extensive panel of human cancer cell lines and against the MV4-11 AML cell line. These molecules were designed as drug-like derivatives of the resveratrol analogue DMU-212 and its cyano derivatives. Four compounds 8g, 8h, 10a and 10b exhibited LD50 values of 4.60 µM, 0.02 µM, 1.46 µM, and 1.08 µM, respectively, against MV4-11 leukemia cells. The most potent compounds, 8h and 10b, were also found to be active against an extensive panel of human hematological and solid tumor cell lines; compound 8h was the most potent compound with GI50 values <10 nM against more than 90% of the human cancer cell lines in the 60-cell panel. Analogues 8g, 8h, 10a and 10b were also tested for their ability to inhibit the polymerization of tubulin, and compound 8h was found to be the most potent analogue. Molecular modeling studies demonstrated that 8h binds to the colchicine binding site on tubulin. Thus, compound 8h is considered to be a lead druglike molecule from this tetrazole series of compounds.

中文翻译：

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白藜芦醇的新型四唑类似物是有效的抗癌剂。

合成了一系列新的白藜芦醇四唑类似物，并评估了其对多种人类癌细胞系和MV4-11 AML细胞系的抗白血病活性。这些分子被设计为白藜芦醇类似物DMU-212及其氰基衍生物的类药物衍生物。四种化合物8g，8h，10a和10b对MV4-11白血病细胞的LD50值分别为4.60 µM，0.02 µM，1.46 µM和1.08 µM。还发现最有效的化合物8h和10b对大量的人类血液学和实体瘤细胞系具有活性。化合物8h是针对60细胞小组中90％以上的人类癌细胞系，其GI50值<10 nM的最有效化合物。类似物8g，8h，还测试了10a和10b抑制微管蛋白聚合的能力，并且发现化合物8h是最有效的类似物。分子模型研究表明，8h与微管蛋白上的秋水仙碱结合位点结合。因此，化合物8h被认为是该四唑系列化合物中的前药样分子。