Background: Mixed ligand-metal complexes are efficient chelating agents because of their flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance.

Methods: Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide (2- butanone thiosemicarbazone) with pyridine, bipyridine and 2-picoline as co-ligands were synthesized with Cu, Co and Zn salts. The complexes were tested against MDA-MB231 (MDA) and A549 cell lines. Antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The drug character of the complexes was evaluated on parameters viz. physicochemical properties, bioactivity scores, toxicity assessment and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile using various automated softwares. Molecular docking was performed against Ribonucleotide Reductase (RR) and topoisomerase II (topo II).

Results: The mixed ligand-metal complexes were synthesized by condensation reaction for 4-5 h. The characterization was done by elemental analysis, 1H-NMR, FT-IR, molar conductance and UV spectroscopic techniques. Molecular docking results showed that [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2], [Zn(C₅H₁₁N₃S)(bpy)(SO₄)] and [Zn(C₅H₁₁N₃S)(2-pic)2(SO4)] displayed the lowest binding energies with respect to RR. Against topo II [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2], [Cu(C₅H₁₁N₃S)(bpy)(CH3COO)2] and [Zn(C₅H₁₁N₃S)(2-pic)2(SO₄)] had the lowest energies. The druglikness assessment was done using Leadlikeness and Lipinski’s rules. Not more than two violations were obtained in case of each filtering rule showing drug-like character of the mixed ligand complexes. Some of the complexes exhibited positive bioactivity scores and almost all the complexes were predicted to be safe with no hazardous effects as predicted by the toxicity assessment. Ames test predicted the non-mutagenic nature of the complexes.

Conclusion: In vitro activity evaluation showed that [Zn(C₅H₁₁N₃S)(py)2(SO₄)], [Co(C₅H₁₁N₃S(bpy) (Cl)2] and [Cu(C₅H₁₁N₃S)(2-pic)2(CH3COO)2] were active against MDA. Against A549 [Co(C₅H₁₁N₃S)(py)2(Cl)2], [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2] and [Co(C₅H₁₁N₃S(bpy)(Cl)2] were active. Antibacterial evaluation showed that [Co(C₅H₁₁N₃S)(bpy)(Cl)2], [Zn(C₅H₁₁N₃S)(2-pic)2(SO₄)] and [Cu(C₅H₁₁N₃S)(2-pic)2(CH3COO)2] were active against S. aureus. Against E. coli, [Zn(C₅H₁₁N₃S)(2- pic)2(SO₄)] showed activity at 18-20 mg dose range.

背景：混合配体-金属配合物是有效的螯合剂，因为它们具有灵活的供体能力。已经探索了含有杂原子硫、氮和氧的混合配体配合物的生物学意义。

方法：以 Cu、Co 和 Zn 盐为共配体，合成了 9 种 2-（丁-2-亚基）肼碳硫酰胺（2-丁酮缩氨基硫脲）与吡啶、联吡啶和 2-甲基吡啶的混合配体-金属配合物。针对 MDA-MB231 (MDA) 和 A549 细胞系测试了复合物。测试了对金黄色葡萄球菌和大肠杆菌的抗菌活性。复合物的药物特性根据参数进行评估，即。理化特性、生物活性评分、毒性评估和吸收、分布、代谢、排泄和毒性 (ADMET) 曲线使用各种自动化软件。针对核糖核苷酸还原酶 (RR) 和拓扑异构酶 II (topo II) 进行分子对接。

结果：通过缩合反应4-5h合成了混合配体-金属配合物。通过元素分析、1H-NMR、FT-IR、摩尔电导和紫外光谱技术进行表征。分子对接结果表明[Cu(C ₅ H ₁₁ N ₃ S)(py)2(CH3COO)2]、[Zn(C ₅ H ₁₁ N ₃ S)(bpy)(SO ₄ )]和[Zn(C ₅ H ₁₁ N ₃ S)(2-pic)2(SO4)] 显示出相对于 RR 的最低结合能。针对拓扑 II [Cu(C ₅ H ₁₁ N ₃ S)(py)2(CH3COO)2]，[Cu(C ₅ H ₁₁ N)₃ S)(bpy)(CH3COO)2] 和[Zn(C ₅ H ₁₁ N ₃ S)(2-pic)2(SO ₄ )] 的能量最低。药物相似性评估是使用 Leadlikeness 和 Lipinski 规则完成的。在每个过滤规则显示混合配体复合物的类药物特征的情况下，获得不超过两次违规。一些复合物表现出积极的生物活性评分，并且几乎所有的复合物都被预测为安全的，正如毒性评估所预测的那样没有危险影响。Ames 检验预测了复合物的非诱变性质。

结论：体外活性评价表明[Zn(C ₅ H ₁₁ N ₃ S)(py)2(SO ₄ )]、[Co(C ₅ H ₁₁ N ₃ S(bpy) (Cl)2]和[Cu) (C ₅ H ₁₁ N ₃ S)(2-pic)2(CH3COO)2] 对 MDA 有活性。对 A549 [Co(C ₅ H ₁₁ N ₃ S)(py)2(Cl)2]、[Cu (C ₅ H ₁₁ N ₃ S)(py)2(CH3COO)2] 和 [Co(C ₅ H ₁₁ N ₃ S(bpy)(Cl)2] 具有活性。抗菌评估表明 [Co(C ₅ H)₁₁ N ₃ S)(bpy)(Cl)2]、[Zn(C ₅ H ₁₁ N ₃ S)(2-pic)2(SO ₄ )] 和 [Cu(C ₅ H ₁₁ N ₃ S)(2 -pic)2(CH3COO)2] 对金黄色葡萄球菌有活性。针对大肠杆菌，[Zn(C ₅ H ₁₁ N ₃ S)(2-pic)2(SO ₄ )] 在 18-20 mg 剂量范围内显示出活性。