Aljohani Ahmed K B, Almadani Sara A, Alsulaimany Marwa, Aljuhani Naif, Samman Waad A, Al-Shareef Adel H, Alghamdi Read, Tayeb Saeed M, Alharbi Hussam Y, Aljohani Majed S, El-Adl Khaled, Salem Mo'men
Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, 42353, Medina, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, 42353, Medina, Saudi Arabia.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 11. doi: 10.1007/s00210-025-04052-8.
Newly synthesized compounds 7, 8, and 9 and their nanogels as nano-carrier drug delivery systems have been synthesized and estimated for their cytotoxicity on MCF-7, HCT-116, HepG2, and A549. This research emphasizes on the formation and description of the Cs/PVA nanogel loaded with our derivatives 7, 8, and 9. The stability of nanogel formation was elucidated by zeta potential values which remained negative with values of -6.8, -11.8, and -7.8 mV respectively. The obtained compounds and their nanogels were evaluated as Topo-II inhibitors and DNA intercalators. The nanogel for compound 7 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 35.93%, 34.29%, 50.91%, and 49.94% respectively. Moreover, the nanogel for compound 8 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 31.13%, 34.09%, 49.59%, and 46.43% respectively. Furthermore, the nanogel for compound 9 enhanced cytotoxicity in A549, HCT116, MCF-7, and HepG2 cancers by 38.99%, 43.78%, 58.25%, and 57.73% respectively. Moreover, our derivatives 7, 7 (nanogel), 8, 8 (nanogel), 9 and 9 (nanogel) exhibited high selectivity against cancer cells and lower toxicity on VERO cells with IC = 45.90-49.90 μM. Furthermore, the new derivatives demonstrated in silico very good anticipated ADMET profile. The nano-carrier formulations for the new derivatives may be purposeful as a prototype for future design, optimization, adaptation and investigation to obtain farther powerful selective anticancer agents.
新合成的化合物7、8和9及其作为纳米载体药物递送系统的纳米凝胶已被合成，并评估了它们对MCF-7、HCT-116、HepG2和A549细胞的细胞毒性。本研究着重于负载我们的衍生物7、8和9的Cs/PVA纳米凝胶的形成与描述。通过zeta电位值阐明了纳米凝胶形成的稳定性，其值分别为-6.8、-11.8和-7.8 mV，均保持为负值。所获得的化合物及其纳米凝胶被评估为拓扑异构酶II抑制剂和DNA嵌入剂。化合物7的纳米凝胶在A549、HCT116、MCF-7和HepG2癌症中分别将细胞毒性提高了35.93%、34.29%、50.91%和49.94%。此外，化合物8的纳米凝胶在A549、HCT116、MCF-7和HepG2癌症中分别将细胞毒性提高了31.13%、34.09%、49.59%和46.43%。此外，化合物9的纳米凝胶在A549、HCT116、MCF-7和HepG2癌症中分别将细胞毒性提高了38.99%、43.78%、58.25%和57.73%。此外，我们的衍生物7、7（纳米凝胶）、8、8（纳米凝胶）、9和9（纳米凝胶）对癌细胞表现出高选择性，对VERO细胞的毒性较低，IC值为45.90 - 49.90 μM。此外，新衍生物在计算机模拟中显示出非常好的预期ADMET特性。新衍生物的纳米载体制剂可能有目的地作为未来设计、优化、调整和研究的原型，以获得更强大的选择性抗癌剂。
