Purpose

The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250.

Methods

The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects.

Results

The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity.

Conclusion

Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.

中文翻译：

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氧噻嗪烷衍生物具有抗肿瘤和抗菌活性：结构活性研究

目的

氧噻嗪烷物质类别的特点是化学结构高度多样化，但尚未得到充分研究。我们的研究小组最近证明，1.4.5-恶噻嗪-4.4-二氧化物（GP-2250）具有抗胰腺癌的特性。本研究旨在深入了解一系列不同氧噻嗪类药物的结构和活性关系，了解其抗肿瘤活性以及与抗菌活性的潜在相关性。我们研究了新合成的氧噻嗪烷衍生物：2255、2256、2287、2289、2293 和 2296，并与 GP-2250 进行比较。

方法

通过体外活力、增殖和细胞迁移测定，评估了不同癌症实体（乳腺癌、皮肤癌、胰腺癌和结肠癌细胞系）的抗肿瘤作用。对各种细菌菌株进行纸片扩散测试以检查抗菌潜力。此外，还进行了活性氧（ROS）测定以研究机制方面。

结果

GP-2250、2293、2289 和 2296 物质不仅在四种不同的癌症实体中显示出抗肿瘤活性，而且在包括 MRSA（耐甲氧西林金黄色葡萄球菌）在内的多种细菌菌株上进行了测试，还显示出抗菌作用。此外，与未处理的对照细胞相比，这些物质还在处理的癌细胞系中诱导了高达 110% 的高 ROS 水平。这些结果表明这些衍生物的抗肿瘤能力和抗菌特性之间存在相关性。这两项活动似乎都是 ROS 驱动的。氧噻嗪烷衍生物2255、2256和2287缺乏抗肿瘤和抗菌活性。

结论

因此，抗肿瘤和抗菌活性的可比较的结构活性关系变得明显。