通过 sp3-CH 激活作为潜在结肠癌抑制剂的新型三环和角四环苯并噻二嗪的合成和分子对接研究,Journal of Heterocyclic Chemistry

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通过 sp3-CH 激活作为潜在结肠癌抑制剂的新型三环和角四环苯并噻二嗪的合成和分子对接研究
Journal of Heterocyclic Chemistry ( IF 2.0 ) Pub Date : 2023-08-14 , DOI: 10.1002/jhet.4715
Sherif O. Kolade _{1,

2} , Oluwafemi S. Aina ₁ , Allen T. Gordon ₂ , Eric C. Hosten ₂ , Idris A. Olasupo ₁ , Adeniyi S. Ogunlaja ₂ , Olayinka T. Asekun ₁ , Oluwole B. Familoni ₁

Affiliation

本文描述了三环和四环苯并噻二嗪及其衍生物的合成，这些衍生物因其作为生物活性剂的多功能性而闻名。起始原料为N-环氨基-4-取代-2-硝基苯磺酰胺8-16，由4-取代-2-硝基苯磺酰氯1-3和环胺4-7缩合制备。中间体 N-环氨基-4-取代-2-磺酰胺 17-25 是通过使用 10% 钯炭催化剂催化氢化 N-环氨基-4-取代-2-硝基苯磺酰胺 8-16 获得的。然后通过无金属分子内 N-碘代琥珀酰亚胺 (NIS) 介导的自由基氧化sp ³ -CH合成具有潜在生物活性的三环和角四环 1,2,4-苯并噻二嗪二氧化物 26-34N-环氨基-4-取代-2-磺酰胺 17-25 的活化氨基环化。产量从好到极好（68-93%）。对 N-环氨基-4-取代-2-硝基苯磺酰胺 8-16、N-环氨基-4-取代-2-磺酰胺 17-25 以及三环和角四环 1,2,4-苯并噻二嗪二氧化物 26- 进行对接研究34 使用五种蛋白质分子治疗结肠癌。结果表明，大部分制备的配体表现出比参比药物卡培他滨、卡培他滨和氟尿嘧啶更高的活性。在合成的化合物中，KS7（一种苯并噻二嗪）显示出针对 6KRO 的最佳活性。

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Synthesis and molecular docking studies of novel tricyclic and angular tetracyclic benzothiadiazines via sp3-C-H activation as potential colon cancer inhibitors

This paper describes the synthesis of tricyclic and tetracyclic benzothiadiazines and their derivatives, which are known for their versatility as bioactive agents. The starting materials were N-cycloamino-4-substituted-2-nitrobenzenesulfonamides 8–16, which were prepared through the condensation of 4-substituted-2-nitrobenzenesulfonyl chlorides 1–3 and cyclic amines 4–7. The intermediates, N-cycloamino-4-substituted-2-sulfanilamides 17–25, were obtained through catalytic hydrogenation of N-cycloamino-4-substituted-2-nitrobenzenesulfonamides 8–16 using a 10% palladium-on-charcoal catalyst. The potentially bioactive tricyclic and angular tetracyclic 1,2,4-benzothiadizine dioxides 26–34 were then synthesized via metal-free intramolecular N-iodosuccinimide (NIS)-mediated radical oxidative sp³-C-H activation aminative cyclization of N-cycloamino-4-substituted-2-sulfanilamides 17–25. The yields were good to excellent (68–93%). Docking studies were conducted for N-cycloamino-4-substituted-2-nitrobenzenesulfonamides 8–16, N-cycloamino-4-substituted-2-sulfanilamides 17–25, and tricyclic and angular tetracyclic 1,2,4-benzothiadizine dioxides 26–34 for colon cancer using five protein molecules. The results showed that most of the prepared ligands exhibited higher activity than the reference drugs capecitabine, capecitabine, and fluorouracil. Among the compounds synthesized, KS7, a benzothiadiazine, showed the best activity against 6KRO.

更新日期：2023-08-14

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