Sunitha Kumari M, Harish Kumar M, Deevith D V, Devarajegowda H C, Palakshamurthy B S
Department of Physics Yuvaraja's College University of Mysore,Mysore 570005 Karnataka India.
Dr. B. R. Ambedkar Medical College, Gandhi nagar, Kadugondanahalli, Bangalore-560045, Karnataka, India.
Acta Crystallogr E Crystallogr Commun. 2025 Feb 25;81(Pt 3):257-263. doi: 10.1107/S2056989025001550. eCollection 2025 Mar 1.
The title compound, CHNO, was synthesized by S2 reaction of bromo-methyl coumarin with 4,4-di-methyl-piperidine-2,6-dione. The mol-ecule crystalizes in the monoclinic system with space group 2/. The coumarin unit is almost planar with a dihedral angle between the aromatic rings of 0.81 (2)° and an r.m.s deviation of 0.042 Å. The piperidine ring adopts a chair conformation with the two methyl groups, one methyl group occupying an axial position and the other an equatorial position, exhibiting maximum stability. In the crystal, C-H⋯O inter-actions lead to the formation of head-to-head dimers with an (8)graph-set motif and (9) and (10) ring motifs along [001] and [100]. π-π inter-actions [centroid-centroid distances = 3.885 (2) and 3.744 (2) Å] are also observed. A Hirshfeld surface analysis was carried out, with the two-dimensional fingerprint plots indicating that the major contributions to the crystal packing are from H⋯H(57%), O⋯H(29.3%) and C⋯H(8.1%) inter-actions. The energy framework calculations reveal that dispersion energy ( = -267.7 kJ mol) dominates the other energies. The mol-ecular structure was optimized by density functional theory calculations using the B3LYP/6-311+G(d,p) basis set. The HOMO and LOMO orbitals were generated to determine the energy gap, which is 4.245 eV. Mol-ecular docking studies were carried out for the title mol-ecule as ligand and a protein as receptor giving binding affinities of -9.5 kcal mol for PDB ID: 5HG8 and -8.2 kcal mol for PDB ID:6 NLV. The compound was further subjected to biological studies against human cancer cell lines, namely cryopreserved triple negative human breast adenocarcinoma cells (MDA-MB-231cells) and adenocarcinomic human alveolar basal epithelial cells (A549 cells) giving ICvalues of 11.57 and 9.34 µ, respectively. The cytotoxicity results showed a good safety profile against HEK293 cell lines.
标题化合物CHNO是通过溴甲基香豆素与4,4 - 二甲基哌啶 - 2,6 - 二酮的S2反应合成的。该分子结晶于单斜晶系，空间群为2/。香豆素单元几乎呈平面状，芳环之间的二面角为0.81 (2)°，均方根偏差为0.042 Å。哌啶环呈椅式构象，两个甲基，一个甲基占据轴向位置，另一个占据赤道位置，表现出最大稳定性。在晶体中，C - H⋯O相互作用导致形成头对头二聚体，具有(8)图形集基序以及沿[001]和[100]的(9)和(10)环基序。还观察到π - π相互作用[质心 - 质心距离 = 3.885 (2)和3.744 (2) Å]。进行了 Hirshfeld 表面分析，二维指纹图谱表明晶体堆积的主要贡献来自H⋯H(57%)、O⋯H(29.3%)和C⋯H(8.1%)相互作用。能量框架计算表明色散能( = -267.7 kJ mol)主导其他能量。使用B3LYP/6 - 311 + G(d,p)基组通过密度泛函理论计算对分子结构进行了优化。生成了HOMO和LOMO轨道以确定能隙，其为4.245 eV。对标题分子作为配体和一种蛋白质作为受体进行了分子对接研究，对于PDB ID: 5HG8的结合亲和力为 -9.5 kcal mol，对于PDB ID: 6NLV的结合亲和力为 -8.2 kcal mol。该化合物进一步针对人类癌细胞系进行了生物学研究，即冷冻保存的三阴性人乳腺腺癌细胞(MDA - MB - 231细胞)和人肺泡基底上皮腺癌细胞(A549细胞)，IC值分别为11.57和9.34 µ。细胞毒性结果显示对HEK293细胞系具有良好的安全性。
