Kaur Harmeet, Singh Jasbir, Narasimhan Balasubramanian
1Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001 India.
2College of Pharmacy, Postgraduate Institute of Medical Sciences, Rohtak, 124001 India.
BMC Chem. 2019 Jul 9;13(1):87. doi: 10.1186/s13065-019-0596-5. eCollection 2019 Dec.
In continuation of our work, new diazenyl chalcones scaffolds ( to ) were efficiently synthesized from substituted acetophenone azo dyes (-) by base catalyzed Claisen-Schmidt condensation with different substituted aromatic/heteroaromatic aldehydes.
The synthesized chalcones were assessed for their in vitro antimicrobial potential towards several pathogenic microbial strains by tube dilution method and further evaluated for antioxidant potential by DPPH assay. These derivatives were also assessed for the cytotoxicity towards the human lung cancer cell line (A549) and normal cell line (HEK) by MTT assay. The most active antimicrobial compounds were docked using Schrodinger 18.1 software with the various potential bacterial receptors to explore the mechanism of interaction.
The derivative exhibited high antibacterial activity with very low MIC (1.95-3.90 µg ml) and MBC (3.90-7.81 µg ml) values. The derivatives , and have demonstrated good antioxidant potential (IC = 7-18 µg ml) correlated to the ascorbic acid (IC = 4.45 µg ml). The derivative had shown comparable cytotoxicity to camptothecin against A549 cell line. The docking studies predicted the bacterial dihydrofolate reductase (PDB ID: 3SRW) and bacterial DNA gyrase (PDB ID: 4ZVI) as the possible targets for most of the active antimicrobial compounds. These derivatives affirmed their safety by presenting less cytotoxicity towards HEK cells. Further the ADME prediction by qikprop module of the Schrodinger proved that these compounds exhibited drug-like attributes.
Hence, these compounds have shown their potential as lead for future expansion of novel antimicrobial and cytotoxic drugs.
在我们的工作延续中，新型重氮基查尔酮支架（to）通过碱催化的克莱森 - 施密特缩合反应，由取代苯乙酮偶氮染料（-）与不同取代的芳香族/杂环芳香醛高效合成。
通过试管稀释法评估合成的查尔酮对几种致病微生物菌株的体外抗菌潜力，并通过DPPH测定法进一步评估其抗氧化潜力。还通过MTT测定法评估这些衍生物对人肺癌细胞系（A549）和正常细胞系（HEK）的细胞毒性。使用Schrodinger 18.1软件将最具活性的抗菌化合物与各种潜在的细菌受体对接，以探索相互作用机制。
衍生物表现出高抗菌活性，最低抑菌浓度（MIC）非常低（1.95 - 3.90μg/ml），最低杀菌浓度（MBC）为（3.90 - 7.81μg/ml）。衍生物、和已显示出良好的抗氧化潜力（IC = 7 - 18μg/ml），与抗坏血酸（IC = 4.45μg/ml）相当。衍生物对A549细胞系显示出与喜树碱相当的细胞毒性。对接研究预测细菌二氢叶酸还原酶（PDB ID：3SRW）和细菌DNA促旋酶（PDB ID：4ZVI）是大多数活性抗菌化合物的可能靶点。这些衍生物对HEK细胞的细胞毒性较小，证实了它们的安全性。此外，Schrodinger的qikprop模块进行的ADME预测证明这些化合物具有类药物属性。
因此，这些化合物已显示出作为未来新型抗菌和细胞毒性药物扩展先导物的潜力。
