Koyambo-Konzapa Stève-Jonathan, Vamhindi Berthelot S D Ramlina, Khudaykulov Bekzod, Sidhom Peter A, Khan Shahzeb, Abdelbacki Ashraf M M, Abdelrahman Alaa H M, Ibrahim Mahmoud A A
Laboratoire Matière, Energie et Rayonnement (LAMER), Université de Bangui, Bangui, République Centrafricaine.
Departement of Physics, Faculty of Science, University of Maroua, Maroua, Cameroon.
PLoS One. 2025 Sep 10;20(9):e0330941. doi: 10.1371/journal.pone.0330941. eCollection 2025.
Polar protic and aprotic solvents can effectively simulate the maturation of breast carcinoma cells. Herein, the influence of polar protic solvents (water and ethanol) and aprotic solvents (acetone and DMSO) on the properties of 3-(dimethylaminomethyl)-5-nitroindole (DAMNI) was investigated using density functional theory (DFT) computations. Thermodynamic parameters retrieved from the vibrational analysis indicated that the DAMNI's entropy, heat capacity, and enthalpy increased with rising temperature. Natural bond orbital computations elucidated the non-bonded interactions of DAMNI. DAMNI demonstrated promising nonlinear optical properties and chemical reactivity in water, with DMSO being the second most effective solvent. Frontier molecular orbitals and global descriptors confirmed the impact of solvents on intermolecular charge transfer. The docking estimations were conducted to predict the docking pose of DAMNI against ERα and EGFR, both of which are acknowledged for their significance in breast cancer treatment. Upon the docking outcomes, DAMNI revealed superior binding affinity against ERα (calc. -5.8 kcal/mol), in comparison with DAMNI against EGFR (calc. -4.7 kcal/mol). Eventually, molecular dynamics simulations (MDS) were carried out, followed by a binding energy computation utilizing the MM/GBSA approach. Upon the MM/GBSA//150 ns MDS, the DAMNI-ERα complex revealed lower binding energy than DAMNI-EGFR, with ΔGbinding values of -21.1 and -15.4 kcal/mol, respectively. Post-MD analyses showed outstanding constancy of the inspected complexes over 150 ns MDS.
极性质子溶剂和非质子溶剂可以有效地模拟乳腺癌细胞的成熟过程。在此，利用密度泛函理论（DFT）计算研究了极性质子溶剂（水和乙醇）和非质子溶剂（丙酮和二甲基亚砜）对3-（二甲基氨基甲基）-5-硝基吲哚（DAMNI）性质的影响。从振动分析中获得的热力学参数表明，DAMNI的熵、热容和焓随温度升高而增加。自然键轨道计算阐明了DAMNI的非键相互作用。DAMNI在水中表现出良好的非线性光学性质和化学反应性，二甲基亚砜是第二有效的溶剂。前线分子轨道和全局描述符证实了溶剂对分子间电荷转移的影响。进行对接估计以预测DAMNI与雌激素受体α（ERα）和表皮生长因子受体（EGFR）的对接构象，这两者在乳腺癌治疗中的重要性已得到认可。根据对接结果，与DAMNI与EGFR的对接（计算值为-4.7 kcal/mol）相比，DAMNI与ERα显示出更高的结合亲和力（计算值为-5.8 kcal/mol）。最终，进行了分子动力学模拟（MDS），随后使用MM/GBSA方法进行结合能计算。在MM/GBSA//150 ns MDS计算中，DAMNI-ERα复合物显示出比DAMNI-EGFR更低的结合能，其ΔGbinding值分别为-21.1和-15.4 kcal/mol。MD后分析表明，在150 ns MDS过程中，所检查的复合物具有出色的稳定性。
