Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur (MS), 413255,India.
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University Aurangabad (MS), 431004,India.
Comb Chem High Throughput Screen. 2022;25(2):274-283. doi: 10.2174/1386207323666201229150734.
The research work aims to synthesize novel series of hydrazones and antioxidant screening. It also aims to evaluate the binding affinities and in silico methods for identifying possible drug targets of synthesized compounds.
This report briefly explains the synthesis of a novel series of hydrazones. It was synthesized via. hydrazinolysis of esters to obtain hydrazide, treated with aldehyde and acetophenone to get hydrazones. The spectral confirmed hydrazones exhibited excellent to comparable anti-oxidant as compared to the standard drugs Butylated hydroxytoluene (BHT) and Ascorbic acid. Molecular docking on myeloperoxidase (MPO) demonstrated the ability of this scaffold to correctly recognize the target and engage in significant bonded and non-bonded interactions with key residues therein.
In this study, we report effectively synthesized compounds BK-35, BK- 41, BK-26, BK-28, and BK-39 that showed the best DPPH radical scavenging activity. The docking results clearly showed the binding mode of hydrazones into the active site of Myeloperoxidase (MPO). In in-silico results, none of the synthesized compounds, BK-24 to BK- 41, violated Lipinski's rule of five (miLog P ≤ 5).
In vitro preliminary anti-oxidant screening results in support by in Silico binding affinity data of novel hydrazones of levofloxacin related molecules BK-24 to BK-41 reported here have emerged as excellent anti-oxidant agents. The inference derived from the in vitro anti-oxidant screening data and the quantitative insights derived from the per-residue interaction analysis with MPO enzyme are now being fruitfully utilized for site-specific mutation around the nucleus to identify selective and potent anti-oxidants.
本研究工作旨在合成新型系列腙类化合物并进行抗氧化筛选。还旨在评估合成化合物的结合亲和力和计算方法，以确定可能的药物靶点。
本报告简要说明了一系列新型腙类化合物的合成方法。通过酯的肼解得到酰肼，然后与醛和苯乙酮反应得到腙。光谱证实，所合成的腙类化合物表现出优异的抗氧化活性，与标准药物丁基化羟基甲苯 (BHT) 和抗坏血酸相当。对髓过氧化物酶 (MPO) 的分子对接表明，该支架具有正确识别靶标的能力，并与其中的关键残基发生显著的键合和非键合相互作用。
在这项研究中，我们报告了有效合成的化合物 BK-35、BK-41、BK-26、BK-28 和 BK-39，它们显示出最佳的 DPPH 自由基清除活性。对接结果清楚地表明了腙类化合物与髓过氧化物酶 (MPO) 活性位点的结合模式。在计算机模拟结果中，没有一个合成化合物（BK-24 到 BK-41）违反了 Lipinski 的五规则（miLog P ≤ 5）。
体外初步抗氧化筛选结果支持这里报道的左氧氟沙星相关分子 BK-24 至 BK-41 的新型腙类化合物的计算机结合亲和力数据，这些化合物已成为优秀的抗氧化剂。从体外抗氧化筛选数据中得出的推论和与 MPO 酶的每个残基相互作用分析得出的定量见解，现在正被有效地用于核周围的定点突变，以确定选择性和有效的抗氧化剂。
