Chalcones and 1,2-benzothiazines are two important classes of bioactive compounds, each scaffold endowed with diverse pharmacological activities. Combining both of these pharmacophores in a single molecule was aimed to yield multi-modal agents. Herein, we report a series of hybrid compounds 3a–3o derived from chalcones and 1,2-benzothiazine cores. They were synthesized from commercially available sodium saccharin, and the resulting 1,2-benzothiazine-derived ketone was then condensed with aromatic aldehydes in an aldol condensation to obtain the respective chalcones. The compounds were characterized using different analytical techniques including FT-IR, NMR spectroscopy, mass spectrometry and X-ray crystallography. Some synthesized chalcones revealed potent and/or selective inhibitory properties towards alkaline phosphatase isozymes transiently expressed in COS-7 cells. A detailed structure-activity and selectivity study was carried out with regard to the effect of different substituents at ortho-, meta- and para-positions of the phenyl residue. Compound 3c was the most effective human intestinal alkaline phosphatase (h-IAP) inhibitor (IC₅₀ value of 1.04 μM), while it was not active against human tissue non-specific alkaline phosphatase (h-TNAP) isozyme. In contrast, 3i was a selective inhibitor of h-TNAP with IC₅₀ values of 0.25 ± 0.01 μM. The possible binding interactions of the most effective inhibitors of h-TNAP and h-IAP were obtained from molecular docking studies.

查耳酮和1,2-苯并噻嗪是两类重要的生物活性化合物，每种支架都具有多种药理活性。将这两个药效基团组合在一个分子中的目的是产生多峰态药物。在此，我们报告了一系列杂化化合物3a – 3o衍生自查耳酮和1,2-苯并噻嗪核。它们由市售糖精钠合成，然后将得到的1,2-苯并噻嗪衍生的酮与芳香醛在醛醇缩合反应中缩合，得到相应的查耳酮。使用不同的分析技术（包括FT-IR，NMR光谱，质谱和X射线晶体学）对化合物进行表征。一些合成的查耳酮显示了对在COS-7细胞中瞬时表达的碱性磷酸酶同工酶的有效和/或选择性抑制特性。针对邻位，间位和对位不同取代基的影响，进行了详细的结构活性和选择性研究苯基残基的-位。化合物3c是最有效的人体肠道碱性磷酸酶（h -IAP）抑制剂（IC ₅₀值为1.04μM），而对人体组织非特异性碱性磷酸酶（h -TNAP）同工酶没有活性。相反，3i是h -TNAP的选择性抑制剂，IC ₅₀值为0.25±0.01μM。最有效的h -TNAP和h -IAP抑制剂可能的结合相互作用是从分子对接研究中获得的。