A series of substituted thieno[2,3-b:4,5-b′]dipyridine compounds were synthesized based on the reactions of 2-acetyl-3-aminothieno[2,3-b]pyridine derivative 1 with 1,3-bifunctional reagents (malononitrile, cyanoacetamide, acetylacetone, ethyl acetoacetate) and/or DMF-DMA. The frontier molecular orbitals of the produced derivatives were obtained from DFT/B3LYP calculations to investigate their structural and energetic properties. The data revealed that they had a low energy gap (ΔE_H-L), 2.32–3.39 eV, where compounds 3 and 6 displayed the smallest and greatest values, respectively. Meanwhile, the antibacterial activity of synthesized thieno[2,3-b:4,5-b′]dipyridine analogues was tested against four bacterial strains. Derivatives 2, 3, 5 and 8 exhibited good activity against Gram-positive bacteria rather than Gram-negative comparable to the ampicillin drug reference. Also, thienodipyridine analogues 2, 3, 5 and 8 displayed good activity in general, but against Gram-positive rather than Gram-negative bacteria. Meanwhile, the SAR of the synthesized analogues was discussed to describe the effect of their substituents on both two Gram-positive bacteria (S. aureus and B. subtilis) and two Gram-negative bacteria (S. typhimurium and E. coli). Also, the molecular docking estimation was applied on these hybrids to inspect their binding interactions toward the E. coli DNA gyrase B active site (PDB code: 1AJ6).

基于2-乙酰基-3-氨基噻吩并[2,3 - b ]吡啶衍生物1与1,3-双功能试剂（丙二腈、氰基乙酰胺、乙酰丙酮、乙酰乙酸乙酯）和/或 DMF-DMA。从 DFT/B3LYP 计算中获得所产生衍生物的前沿分子轨道，以研究它们的结构和能量特性。_{数据显示它们的能隙 (ΔE H-L} )较低，为 2.32–3.39 eV，其中化合物3和6分别显示最小值和最大值。同时，合成的噻吩并[2,3- b的抗菌活性:4,5- b ']联吡啶类似物针对四种细菌菌株进行了测试。与氨苄青霉素药物参考相比，衍生物 2、3、5和8对革兰氏阳性菌而非革兰氏阴性菌表现出良好的活性。此外，噻吩并二吡啶类似物2、3、5 和 8通常表现出良好的活性，但针对革兰氏阳性菌而不是革兰氏阴性菌。同时，讨论了合成类似物的 SAR 以描述其取代基对两种革兰氏阳性菌（金黄色葡萄球菌和枯草杆菌）的影响) 和两种革兰氏阴性菌（鼠伤寒沙门氏菌和大肠杆菌）。此外，分子对接估计应用于这些杂种，以检查它们对大肠杆菌DNA 促旋酶 B 活性位点（PDB 代码：1AJ6）的结合相互作用。