Department of Chemistry, Faculty of Science, Albaha University, Albaha, Kingdom of Saudi Arabia.
Arch Pharm (Weinheim). 2021 Sep;354(9):e2100021. doi: 10.1002/ardp.202100021. Epub 2021 May 14.
New thiazolidine-2,4-dione hybrids were designed and synthesized as potential peroxisome proliferator-activated receptor (PPAR)-γ agonists and thymidylate synthase inhibitors. All the synthesized compounds follow Lipinski's and Veber's rules and possess the desired pharmacokinetics properties. The PPAR-γ transactivation results displayed that compounds 12 (78.9%) and 11 (73.4%) were the most active compounds and they increased PPAR-γ gene expression by 2.2- and 2.4-fold, respectively. Compounds 12, 11, and 8 showed promising cytotoxicity, with IC values ranging from 1.4 to 4.5 μM against MCF-7 cells and from 1.8 to 8.4 μM against HCT-116 cells. Compounds 11 and 12 also inhibited thymidylate synthase with IC values of 5.1 and 3.2 μM, respectively, confirming their mode of action as thymidylate synthase inhibitors. Finally, molecular docking studies supported the in vitro biological activity results.
新的噻唑烷-2,4-二酮类化合物被设计和合成，作为潜在的过氧化物酶体增殖物激活受体（PPAR）-γ激动剂和胸苷酸合成酶抑制剂。所有合成的化合物都遵循 Lipinski 和 Veber 的规则，并具有所需的药代动力学特性。PPAR-γ 转录激活结果显示，化合物 12（78.9%）和 11（73.4%）是最活跃的化合物，它们分别将 PPAR-γ 基因表达增加了 2.2 倍和 2.4 倍。化合物 12、11 和 8 对 MCF-7 细胞表现出有前途的细胞毒性，IC 值范围为 1.4 至 4.5 μM，对 HCT-116 细胞的 IC 值范围为 1.8 至 8.4 μM。化合物 11 和 12 也抑制胸苷酸合成酶，IC 值分别为 5.1 和 3.2 μM，证实它们作为胸苷酸合成酶抑制剂的作用模式。最后，分子对接研究支持了体外生物学活性结果。
