Post-Graduate Program of Translational Research on Drugs and Medicines, Institute of Drug Technology, Oswaldo Cruz Foundation, Brazil.
Laboratory of Molecular Pharmacology, Department of Pharmacology, Institute of Drug Technology, Oswaldo Cruz Foundation, Brazil.
Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3515-3524. doi: 10.31557/APJCP.2024.25.10.3515.
To evaluate the in vitro and silico antiproliferation of p-cymene, cumin aldehyde, cuminic acid, and cuminol against human cancer cell lines (HCCLs). The sodium salt of the organic acid was included after synthesis.
The quality of the compounds was verified using analytical methods. A primary screening of the compounds at 100 µM was conducted (n=6) on nine HCCLs (SK-MEL-28, K562, Lucena, Jurkat, Caco-2, MDA-MB-231, THP-1, U87-MG, and Calu-3) and HEK-293 through the MTT method after 48h-incubation. The viability curve and apoptotic and necrotic cell populations of cumin aldehyde-treated Calu-3 cells were determined. The statistical significance relative to the vehicle was evaluated using ANOVA and Dunnett. The possibility of being active (Pa) on HCCLs and biological targets was assessed in silico using CLC-Pred. Moreover, the ADMET properties were predicted using three servers.
Only cumin aldehyde induced a low and significant (31±5%, p<0.001) in vitro antiproliferation, and even then, only on the Calu-3 line (IC50 650 µM). Only necrosis was significant (p<0.01) with 300 µM after 24h. The absence (p>0.05) of in vitro activity on the other HCCLs corroborated the low in silico probability of being active (Pa≤0.33), except for cumin aldehyde on the MDA-MB-231 line (Pa=0.47). P-cymene was proven to be the most toxic compound to human health.
Excepting cumin aldehyde, the lack of the antiproliferation potential of these p-cymene derivatives was extensively demonstrated for the first time. Cuminaldehyde induced toxicity in a lung adenocarcinoma line, corroborating the literature. Six selective and three specific cell lines were proposed to evaluate the anticancer activity of the compounds in addressed studies, mainly involving those with Pa≥0.50. The inhibition of five targets seems to play a role in inducing HCCL antiproliferation. The ADMET estimated that cumin aldehyde, cuminol, and sodium cuminate are the safest compounds for human use.
评估对伞花烃、香茅醛、香茅酸和香茅醇对人癌细胞系（HCCL）的体外和计算机模拟抗增殖作用。合成后包括有机酸的钠盐。
使用分析方法验证化合物的质量。在 48 小时孵育后，通过 MTT 法对 9 个人 HCCL（SK-MEL-28、K562、Lucena、Jurkat、Caco-2、MDA-MB-231、THP-1、U87-MG 和 Calu-3）和 HEK-293 进行 100μM 浓度的化合物初步筛选（n=6）。测定香茅醛处理的 Calu-3 细胞的活力曲线和凋亡和坏死细胞群。用方差分析和 Dunnett 评估与载体相比的统计学意义。使用 CLC-Pred 在计算机上评估对 HCCL 和生物靶标具有活性的可能性（Pa）。此外，使用三个服务器预测 ADMET 特性。
只有香茅醛诱导出低而显著的体外增殖抑制作用（31±5%，p<0.001），即使如此，也仅在 Calu-3 系中（IC50 为 650μM）。仅在 24 小时时 300μM 时的坏死有显著差异（p<0.01）。在其他 HCCL 上缺乏体外活性（p>0.05）证实了低计算机模拟活性的可能性（Pa≤0.33），除了香茅醛在 MDA-MB-231 系中（Pa=0.47）。证明对伞花烃是对人体健康最具毒性的化合物。
除香茅醛外，这些对伞花烃衍生物的增殖潜力缺乏首次得到广泛证实。香茅醛在肺腺癌系中引起毒性，与文献一致。提出了六个选择性和三个特异性细胞系来评估化合物在已发表研究中的抗癌活性，主要涉及 Pa≥0.50 的化合物。抑制五个靶标似乎在诱导 HCCL 增殖中起作用。ADMET 估计香茅醛、香茅醇和香茅酸钠对人体使用最安全。
