Elbatrawy Omnia R, Hagras Mohamed, El Deeb Moshira A, Agili Fatimah, Hegazy Maghawry, El-Husseiny Ahmed A, Mokhtar Mahmoud Mohamed, Elkhawaga Samy Y, Eissa Ibrahim H, El-Kalyoubi Samar
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11823, Egypt.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
Pharmaceuticals (Basel). 2023 Jul 6;16(7):966. doi: 10.3390/ph16070966.
: Histone deacetylase inhibitors (HDACIs) are a relatively new class of potential drugs for treating cancer. : Discovery of new anticancer agents targeting HDAC. : New uracil and thiouracil derivatives panels were designed and synthesized as HDAC inhibitors. The synthesized compounds were tested against MCF-7, HepG2, and HCT-116. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. The most active member was tested for its potential against cell cycle, apoptosis, caspase-3, and caspase-8. Docking studies were carried out against HDAC1. : Compounds , , , , , and exhibited promising cytotoxic activities. HDAC1 and HDAC4 inhibitory activities of these compounds were tested. Regarding the HDAC1 inhibitory activity, compound was the most potent member (IC = 0.05 µg/mL) compared to trichostatin A (IC = 0.0349 µg/mL). For HDAC4, compound showed superior activity (IC = 2.83 µg/mL) than trichostatin A (IC = 3.349 µg/mL) Compound showed a high potential to arrest the HCT116 cell cycle at the G0-G1 phase. In addition, it showed an almost 17 times apoptotic effect (37.59%) compared to the control cells (2.17%). Furthermore, Compound showed significant increases in the levels of caspase-3 and caspase-8. Finally, the uracil and thiouracil derivatives showed accepted binding mods against HDAC. : Compound has potential anticancer activity targeting HDAC with a significant apoptotic effect.
组蛋白去乙酰化酶抑制剂（HDACIs）是一类相对新型的潜在抗癌药物。：发现靶向HDAC的新型抗癌剂。：设计并合成了新的尿嘧啶和硫脲嘧啶衍生物作为HDAC抑制剂。对合成的化合物进行了针对MCF-7、HepG2和HCT-116细胞的测试。测试了这些化合物的HDAC1和HDAC4抑制活性。对活性最高的成员进行了其对细胞周期、凋亡、caspase-3和caspase-8的作用潜力测试。针对HDAC1进行了对接研究。：化合物 、 、 、 、 和 表现出有前景的细胞毒性活性。测试了这些化合物的HDAC1和HDAC4抑制活性。关于HDAC1抑制活性，与曲古抑菌素A（IC = 0.0349 µg/mL）相比，化合物 是最有效的成员（IC = 0.05 µg/mL）。对于HDAC4，化合物 显示出比曲古抑菌素A（IC = 3.349 µg/mL）更高的活性（IC = 2.83 µg/mL）。化合物 显示出在G0-G1期阻滞HCT116细胞周期的高潜力。此外，与对照细胞（2.17%）相比，它显示出近17倍的凋亡效应（37.59%）。此外，化合物 显示出caspase-3和caspase-8水平的显著增加。最后，尿嘧啶和硫脲嘧啶衍生物对HDAC显示出可接受的结合模式。：化合物 具有靶向HDAC的潜在抗癌活性，并具有显著的凋亡效应。
