Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC₅₀ = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored − 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and − 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

癌症和不同类型的肿瘤仍然是对现有治疗药物最具抵抗力的疾病。寻找高效的抗癌药物是万千药物设计者的首要目标和关注点。为了解决这个问题，我们通过结构优化设计并合成了一种新的吡嗪衍生物1-(5-溴吡嗪-2-基)-1-[3-(三氟甲基)苄基]脲( BPU )，以研究其抗癌/抗肿瘤潜力。使用选定的细胞系（包括 Jurkat、HeLa 和 MCF-7 细胞）通过 MTT 测定评估BPU的体外抗癌特性。选择 Jurkat 细胞来使用流式细胞术技术研究BPU对细胞周期分析的影响。BPU在所评估的所有三种细胞系中均表现出有效的细胞毒能力。发现 Jurkat 细胞系的情况更为突出 (IC ₅₀  = 4.64 ± 0.08 µM)。当进行细胞周期分析时，该化合物有效地将细胞周期进程抑制在亚 G1 期。通过体内/离体无壳鸡绒毛尿囊膜 (CAM) 测定评估BPU的抗血管生成潜力后，该化合物表现出非常重要的发现，揭示了该化合物通过以下方式作为有效抗癌剂的补充支持作用：抑制肿瘤组织中的血管形成。此外， BPU与人基质金属蛋白酶 2 (MMP-2)的对接能量计算得分为 − 9.0 kcal/mol，与人基质金属蛋白酶 9 (MMP-9) 的对接能量为 − 7.8 kcal/mol，这表明与现有的癌症治疗药物。分子动力学（MD）模拟结果表明，BPU能够有效地结合先前提出的MMP-2和MMP-9酶的催化位点，且状态相对稳定，具有良好的抑制结合能力和参数。我们的研究结果表明，化合物BPU可能是一种有前途的抗癌剂，因为它能有效抑制细胞增殖，并且可以被选择用于进一步的体外和体内研究。此外，目前的结果可以通过湿实验室分析得到广泛验证，从而开发出新的、更好的BPU衍生物用于癌症治疗，副作用更小，活性更高。