Hamed Amany M, Enaili Souhaila S, I Mohammed Walaa, Abouelella Azza M A, Mohana Zeyad Elsayed Eldeeb, Monir Dina M, Soliman Safaa S, Hamouda Elsayed Eldeeb Mehana, Elatif Hytham Mahmoud Abd, El-Saghier Ahmed M
Chemistry Department, Faculty of Science, Sohag University, Sohag 82524, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Zawia, Al Zawia 16418, Libya.
Biomedicines. 2025 Jul 15;13(7):1732. doi: 10.3390/biomedicines13071732.
: Inflammation is a crucial and complex mechanism that protects the body against infections. In our study, we propose to provide scientific evidence for the anti-inflammatory properties of 1,3,5-triazine derivatives. : Initially, we ensured the safety of the three synthesized derivatives by administering graded doses of up to 2000 mg/kg intraperitoneally in Wistar rats. Thus, the three derivatives were considered generally safe. We also evaluated their ability to reduce carrageenan-induced rat paw edema. : Compounds , , and demonstrated stronger anti-inflammatory activity than indomethacin (10 mg/kg), achieving maximum inhibition at the fourth hour with percentages of 96.31%, 72.08%, and 99.69%, respectively, at a dose of 200 mg/kg, compared to 57.66% for the standard drug. To explore the mechanism, levels of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6, CRP) and oxidative stress markers were measured in paw tissue. All three compounds significantly reduced these markers more effectively than indomethacin and enhanced antioxidant levels (SOD and GSH) beyond those achieved by the standard treatment. Additionally, the compounds reduced COX-1 and COX-2 levels to values comparable to those in the normal (non-inflamed) control group. : Compounds , , and at doses of 200 mg/kg significantly ( < 0.05) inhibited the heat-induced hemolysis of red blood cell (RBC) membranes by 94.6%, 93.9%, and 95.2%, respectively, compared to 94.5% produced by indomethacin. Consequently, we concluded that 1,3,5-triazine derivatives are a safe antioxidant agent with significant anti-inflammatory activity.
炎症是一种保护身体免受感染的关键且复杂的机制。在我们的研究中，我们旨在为1,3,5 - 三嗪衍生物的抗炎特性提供科学证据。最初，我们通过在Wistar大鼠腹腔内给予高达2000 mg/kg的分级剂量来确保三种合成衍生物的安全性。因此，这三种衍生物被认为总体安全。我们还评估了它们减轻角叉菜胶诱导的大鼠爪肿胀的能力。化合物 、 和 表现出比吲哚美辛（10 mg/kg）更强的抗炎活性，在200 mg/kg剂量下，在第四小时达到最大抑制，抑制率分别为96.31%、72.08%和99.69%，而标准药物的抑制率为57.66%。为了探究其机制，我们测量了爪组织中促炎细胞因子（TNF-α、IL-1α、IL-1β、IL-6、CRP）水平和氧化应激标志物。所有三种化合物比吲哚美辛更有效地显著降低了这些标志物，并提高了抗氧化水平（SOD和GSH），超过了标准治疗所达到的水平。此外，这些化合物将COX-1和COX-2水平降低至与正常（未发炎）对照组相当的值。化合物 、 和 在200 mg/kg剂量下分别显著（P < 0.05）抑制热诱导的红细胞（RBC）膜溶血94.6%、93.9%和95.2%，而吲哚美辛的抑制率为94.5%。因此，我们得出结论，1,3,5 - 三嗪衍生物是一种具有显著抗炎活性的安全抗氧化剂。
