Aljohani Ahmed K B, El-Hddad Sanadelaslam S A, Alsulaimany Marwa, Maghrabi Nader A, Alhammad Alaa M, Aloufi Mayar N, Alahmadi Luai F, Ali Saeedi Turkiah, Neyaz Yousef Yakoub, Anwer Kurls E, Abd El-Sattar Nour E A, El-Adl Khaled
Department of Pharmacognosy & Pharmaceutical Chemistry, College of Pharmacy, Taibah University Medina 42353 Saudi Arabia.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Omar Almukhtar University Al Bayda 991 Libya.
RSC Adv. 2025 Apr 1;15(13):10037-10048. doi: 10.1039/d5ra00166h. eCollection 2025 Mar 28.
Pyrazole derivatives 2 and 3, pyrimidine derivative 4, and their nanogels as drug delivery systems were synthesized, and their cytotoxicity against MCF-7, HCT-116, HepG2 and A549 cells was evaluated. Herein, we focused on the characterization and synthesis of chitosan/polyvinyl alcohol (Cs/PVA) nanogels loaded with derivatives 2, 3 and 4. The stability of the prepared nanogels 2, 3 and 4 was elucidated by zeta potential measurements, which possessed negative values of -9.7, -1.3 and -1.6 mV, respectively. Our compounds and their nanogels were evaluated as topo-II inhibitors and DNA intercalators. The nanogel delivery system enhanced the cytotoxicity of compound 2 against the A549, HCT116, HepG2 and MCF-7 cancer cell lines by 32.06%, 28.96%, 44.32% and 50.00%, respectively. Moreover, the nanogel of compound 3 exhibited enhanced cytotoxicity against the A549, HCT116, HepG2 and MCF-7 cancer cell lines by 33.61%, 30.64%, 44.69% and 47.86%, respectively. Furthermore, the nanogel of compound 4 showed enhanced cytotoxicity against the A549, HCT116, HepG2 and MCF-7 cancer cell lines by 31.82%, 40.12%, 50.00% and 52.61%, respectively. Moreover, derivatives 2, 2 (nanogel), 3, 3 (nanogel), 4 and 4 (nanogel) exhibited good selectivity against cancer cells and reduced toxicity to VERO cells with IC values in the range of 48.29-59.70 μM. Furthermore, our derivatives displayed remarkable predicted ADMET profiles.
合成了吡唑衍生物2和3、嘧啶衍生物4及其作为药物递送系统的纳米凝胶，并评估了它们对MCF-7、HCT-116、HepG2和A549细胞的细胞毒性。在此，我们重点研究了负载衍生物2、3和4的壳聚糖/聚乙烯醇（Cs/PVA）纳米凝胶的表征与合成。通过zeta电位测量阐明了制备的纳米凝胶2、3和4的稳定性，其zeta电位分别为-9.7、-1.3和-1.6 mV，均为负值。对我们的化合物及其纳米凝胶作为拓扑异构酶II抑制剂和DNA嵌入剂进行了评估。纳米凝胶递送系统使化合物2对A549、HCT116、HepG2和MCF-7癌细胞系的细胞毒性分别提高了32.06%、28.96%、44.32%和50.00%。此外，化合物3的纳米凝胶对A549、HCT116、HepG2和MCF-7癌细胞系的细胞毒性分别提高了33.61%、30.64%、44.69%和47.86%。此外，化合物4的纳米凝胶对A549、HCT116、HepG2和MCF-7癌细胞系的细胞毒性分别提高了31.82%、40.12%、50.00%和52.61%。此外，衍生物2、2（纳米凝胶）、3、3（纳米凝胶）、4和4（纳米凝胶）对癌细胞表现出良好的选择性，对VERO细胞的毒性降低，IC值在48.29 - 59.70 μM范围内。此外，我们的衍生物显示出显著的预测ADMET特征。
