Medicinal Chemistry Group, Chemical Engineering Department, Military Institute of Engineering, Rio de Janeiro, Brazil.
Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro, Brazil.
J Biomol Struct Dyn. 2021 Sep;39(15):5498-5508. doi: 10.1080/07391102.2020.1790419. Epub 2020 Jul 13.
The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one () and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from H, C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs.Communicated by Ramaswamy H. Sarma.
7-氯-9-(2-羟基-4,4-二甲基-6-氧代环己-1-烯-1-基)-3,3-二甲基-2,3,4,9-四氢-1H-呫吨-1-酮（）和 5-[-7-氯-2,4-二氧代-1H,2H,3H,4H,5H-色烯并[2,3-d]嘧啶-5-基)]-1,3-二嗪烷-2,4,6-三酮（）是由二甲基酮和巴比妥酸合成的，通过核磁共振（NMR）从 H、C、APT、COSY、HSQC 和 HMBC 谱获得了它们的三维结构和精确的化学位移分配。额外的 HOMO-LUMO DFT 计算证实了 NMR 结果，并指出了每个化合物最稳定的立体异构体。此外，进一步的对接和分子动力学研究表明，立体异构体（9S）-7-氯-9-(2-羟基-4,4-二甲基-6-氧代环己-1-烯-1-基)-3,3-二甲基-2,3,4,9-四氢-1H-呫吨-1-酮和 5-[(5S)-7-氯-2,4-二氧代-1H,2H,3H,4H,5H-色烯并[2,3-d]嘧啶-5-基)]-1,3-二嗪烷-2,4,6-三酮可能作为 DNA 嵌入剂，作为开发新的抗癌药物的潜在先导化合物。由 Ramaswamy H. Sarma 传达。
