Laboratorio de MicroRNAs y Cáncer, Universidad Autónoma de Zacatecas, Av. Preparatoria S/N, Agronómica, Campus II, Zacatecas, Zac., 98066, México.
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Campus Guanajuato, Noria Alta S/N, Guanajuato, 36050, México.
Curr Med Chem. 2024;31(38):6306-6318. doi: 10.2174/0109298673292365240422104456.
A family of 4-benzo[][1,3]oxazines were obtained from a group of -(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6--dig C-O cyclization.
The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4-benzo[][1,3]oxazines showed an IC rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells.
We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation.
These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.
通过金（I）催化的化学选择性 6-位-π-芳炔 C-O 环化反应，从一组 -（2-炔基）芳基苯甲酰胺前体中得到了一系列 4-苯并[][1,3]恶嗪。
研究了前体和恶嗪在乳腺癌细胞系 MCF-7、CAMA-1、HCC1954 和 SKBR-3 中的活性，发现具有芳基取代基的分子在 C-2 位的化合物具有不同程度的抑制作用，表现出不同的生物活性。4-苯并[][1,3]恶嗪在 MCF-7 中的 IC 为 0.30 至 157.4 µM，在 CAMA-1 中为 0.16 至 139 µM，在 SKBR-3 中为 0.09 至 93.08 µM，在 HCC1954 中为 0.51 至 157.2 µM。
我们观察到依托泊苷类似于苯并恶嗪，而紫杉醇的作用更强。四种细胞系对苯并恶嗪有反应，而 SKBR-3 细胞系对前体和苯并恶嗪有反应。化合物 16、24、25 和 26 在四种细胞系的细胞增殖抑制中具有较强的作用，并与氧化活性相关，提示可能通过 ROS 生成产生了一种可能的机制。
这些化合物代表了治疗乳腺癌的潜在药物候选物。然而，需要进一步的试验来阐明其对癌症细胞和分子特征的全面影响。
