Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
Bioorg Chem. 2019 Jul;88:102968. doi: 10.1016/j.bioorg.2019.102968. Epub 2019 Apr 30.
New quinoline-3-carbonitrile derivatives were synthesized and evaluated for their potential antibacterial behavior. Compounds were obtained by a one-pot multicomponent reaction of appropriate aldehyde, ethyl cyanoacetate, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one and ammonium acetate. Structures were established by different physical and spectroscopic techniques. The molecular geometry, vibration frequencies, HOMO-LUMO energy gap, molecular hardness (g), ionization energy (IE), electron affinity (EA), and total energy of these compounds was assessed by DFT studies, employing DFT/RB3LYP method. Preliminary antibacterial studies using both Gram-positive and Gram-negative bacterial strains and cytotoxicity studies on mammalian cells revealed their promising antibacterial activity, without causing any severe host toxicity. All the compounds (QD1-QD5) in this study obeyed the 'Lipinski's Rule of Five' with logP values <5 and HBA <10, hydrogen bond donor's <5. The most active compound QD4 showed good interaction with the target DNA gyrase; target enzyme for quinoline class of antibiotics, which reveals its probable mechanism of action. Results of all these studies establish these compounds as important scaffolds with broad-spectrum antibacterial activity with no off-target toxicity. Having lower band gap energy of 3.40 eV and a low lying LUMO for compound QD4, this compound may be a valuable starting point for the development of quinoline-3-carbonitrile based broad-spectrum antibacterial agents.
新的喹啉-3-甲腈衍生物被合成并评估其潜在的抗菌行为。化合物通过适当的醛、氰基乙酸乙酯、6-甲氧基-1,2,3,4-四氢-萘-1-酮和乙酸铵的一锅多组分反应获得。通过不同的物理和光谱技术确定了结构。通过使用 DFT/RB3LYP 方法的 DFT 研究评估了这些化合物的分子几何形状、振动频率、HOMO-LUMO 能隙、分子硬度（g）、电离能（IE）、电子亲合能（EA）和总能量。初步的抗菌研究使用革兰氏阳性和革兰氏阴性细菌菌株以及对哺乳动物细胞的细胞毒性研究表明它们具有有希望的抗菌活性，而不会引起任何严重的宿主毒性。本研究中的所有化合物（QD1-QD5）都遵守“Lipinski's Rule of Five”，具有 <5 的 logP 值和 <10 的 HBA，氢供体 <5。最活性化合物 QD4 与喹啉类抗生素的靶标 DNA 拓扑异构酶表现出良好的相互作用，这揭示了其可能的作用机制。所有这些研究的结果都表明这些化合物作为具有广谱抗菌活性且无脱靶毒性的重要支架。化合物 QD4 的带隙能为 3.40 eV，LUMO 较低，因此可能是基于喹啉-3-甲腈的广谱抗菌剂开发的有价值的起点。
